Mapping the Optimal Supply Chain for Biologics, from Formulation to Clinic

Summary

本日のウェビナーでは、バイオロジカルの最適なサプライチェーンマッピングに関する議論が行われました。Sharp ClinicalとBerkshire Sterile Manufacturingの専門家が、バイオロジカルの製造から臨床までの供給網の要素、課題、および解決策について詳述。臨床試験市場の成長戦略、パートナーの選定、そして臨床試験の複雑さを軽減する方法が重点的に紹介されました。ウェビナーは、参加者が質疑応答セッションを通じてスピーカーと積極的に対話することを促しました。

Takeaways

• 😀 このウェビナーでは、生物製剤の最適なサプライチェーンについて説明します。
• 🤔 ウェビナーは60分間で、プレゼンテーションとQ&Aセッションが含まれます。
• 📊 生物製剤の市場は急速に成長しており、特に臨床試験と商業化において重要な役割を果たしています。
• 💊 伝統的な医薬品と比較して、生物製剤のサプライチェーンは複雑で、多くの特別な取り扱いが必要です。
• 🧊 温度管理が重要で、冷蔵および冷凍の取り扱いが必要となる場合があります。
• 📦 適切なサプライチェーンパートナーの選定が、成功するための鍵です。
• 💡 製造プロセス、ラベル付け、包装、物流など、各段階での計画と準備が重要です。
• 🕵️‍♂️ サプライチェーンの途中で複数のベンダーを管理することが、時間と予算の消費を引き起こす可能性があります。
• 📝 ウェビナー中に、製造業者と契約する際に重要な質問や考慮事項が紹介されました。
• 📈 サプライチェーンをスムーズにするためには、早期からパートナーと協力し、明確なコミュニケーションを取ることが不可欠です。

Q & A

セミナーの主題は何ですか？

セミナーの主題は「生物制剂の最適なサプライチェーン：配方から診療所まで」です。

セミナーで紹介されたシャープ臨床のどのような役割がありますか？

シャープ臨床は、薬品およびバイオテクノロジークライアント向けのパッケージングや高度な臨床サプライチェーンサービスを提供するグローバルリーダーです。

サシャ・ソネンバーグがシャープ臨床に加入した時期と役職は何ですか？

サシャ・ソネンバーグは2019年9月にシャープ臨床に加入し、臨床試験市場における成長戦略を支援するグローバルビジネス開発責任者になりました。

アンドレア・ワグナーが設立した会社とその特長は何ですか？

アンドレア・ワグナーはバークシャー・ステアル製造を共同設立し、市場で求められていた未解決の需要に応えるためにユニークな隔離器ベースの柔軟なフィルラーを効果的に開発して、同業中脱颖而出しました。

セミナーで説明された生物制剂のサプライチェーンの特徴は何ですか？

生物制剂のサプライチェーンは、伝統的な医薬品のサプライチェーンと比較して、生体組織や細胞を含むliving organismsを扱うことが多々あるため、より複雑で管理が困難です。

セミナーで強調された「最適なパートナーを見つける」プロセスには何が含まれますか？

「最適なパートナーを見つける」プロセスには、パートナーの能力とサービスを理解するための質問の提唱、情報収集、要求情報(RFI)と提案要求書(RFP)の評価、見積もりの収集、最適なパートナーの選択が含まれます。

セミナーで説明された臨床試験サプライチェーンのどの段階で最も注意が必要ですか？

セミナーでは、計画と準備、分析と配方製造、一次包装、二次包装、保管と配送、実行とレビューの各段階で注意が必要ですが、特に計画と準備の段階で詳細な情報共有とコミュニケーションが重要です。

セミナーで提供されたポルの結果によると、参加者が最も関心を持っている点は何ですか？

ポルの結果によると、参加者は「品質システムと安定性の保証」に最も関心を持っており、次に「タイトなタイムラインの遂行」が続きました。

セミナーで説明された、CMOとの協力を円滑に進めるためのポイントは何ですか？

セミナーでは、CMOとの協力を円滑に進めるためのポイントとして、コミュニケーションの重要性、期待の管理、そして早期にパートナーを巻き込むことなどが説明されました。

セミナーで紹介された、生物制剂のグローバルな薬剤販売における動向はどうでしたか？

セミナーでは、2016年から2024年までの期間で生物技術製品の販売が増加し、特に生物制剂は全球的なブロックバスターの中で最も価値があると示されました。

Outlines

00:00

👋 ウェビナーの開始と概要

本日のウェビナーのタイトルと目的、司会の紹介、ウェビナーの構成と参加者の参加方法について説明しています。また、スポンサー企業であるSharp Clinicalの紹介も行っています。Sharp Clinicalはグローバルな契約製薬包装および臨床供給チェーンサービスのリーダーです。

05:01

📊 グローバルな薬品市場とバイオロジクスの重要性

バイオロジクス市場の成長とその重要性についてのデータを共有しています。特に、グローバルな薬品売上の中でのバイオロジクスの優位性や、その高価な治療コスト、慢性疾患に対する使用などに焦点を当てています。また、バイオロジクス供給チェーンの独自性とその影響についても触れています。

10:02

🔍 バイオロジクス供給チェーンの課題と対策

バイオロジクスの供給チェーンにおける様々な課題について詳述しています。特に、複雑なプロトコル、患者登録のリードタイム、国ごとの規制、冷蔵管理の必要性、物流の課題、複数のベンダー管理などについて説明しています。これらの課題に対する具体的な対策や、臨床試験供給チェーンの計画と準備についても触れています。

15:03

🤝 最適なCMOパートナーの選定と重要な質問

最適なCMO（契約製造機関）パートナーを選定する際の重要な考慮事項について説明しています。具体的には、タイミング、品質、アナリティカルテスト、製剤、ラベル付け、分配などの要素を含む質問のリストを提供しています。また、CMOとスポンサーの間での効果的なコミュニケーションの重要性についても強調しています。

20:04

🏗️ プロセスエンジニアリングと製造の役割

プロセスエンジニアリンググループ、品質管理グループ、品質保証グループ、製造グループなど、製品の製造プロセスに関与する主要なグループの役割について説明しています。各グループの具体的な責任や、計画と準備段階での重要なタスクについて詳述しています。

25:05

🚀 実行フェーズと品質管理

製造プロセスの実行フェーズについて説明しています。具体的には、プロセスエンジニア、製造チーム、品質管理チーム、品質保証チームがどのように連携して製品を製造し、品質を確保するかについて詳述しています。また、実行フェーズ中の重要なタスクや、デバイエーションを防ぐためのバッチレコードの承認の重要性についても触れています。

30:07

📦 販売後の品質管理とキッティング

製品の出荷後の品質管理プロセスについて説明しています。具体的には、品質管理グループがどのようにして最終的なリリーステストを行い、品質保証グループがどのようにしてすべての記録を確認し、コンプライアンス証明書を発行するかについて詳述しています。また、キッティングと分配プロセスについても触れています。

35:07

📝 契約と品質保証の重要性

契約を結ぶ前に考慮すべき技術的、品質的、タイミングの要素について説明しています。具体的には、すべての質問に対して十分な回答を得ること、仕様が満たされることを確認すること、品質文書の迅速かつ徹底的なレビューを行うことの重要性について強調しています。また、契約後のスムーズな移行を確保するためのコミュニケーションの重要性についても触れています。

40:09

❄️ 冷蔵管理と物流の課題

バイオロジクスの供給チェーンにおける冷蔵管理と物流の課題について説明しています。具体的には、デポの選定、輸送と保管の温度管理、包装とモニタリングソリューションの選択、国ごとの輸入許可の取得などについて詳述しています。また、リターンおよび破棄サービスの重要性についても触れています。

45:11

🏢 EUの資格者と輸入手続き

EUにおける資格者（QP）の役割と、輸入手続きの要件について説明しています。具体的には、QPがEUの規制に準拠して製品をリリースするプロセスや、供給チェーン監査の必要性について詳述しています。また、監査のスケジューリングやタイミングへの影響についても触れています。

50:13

📦 比較薬の調達と包装戦略

比較薬の調達と包装戦略について説明しています。特に、比較薬の価格や安定性データ、盲検化戦略、翻訳と規制承認のプロセスについて詳述しています。また、複雑な供給チェーンにおける主要な考慮事項や、適切なパートナーを早期に関与させる重要性についても触れています。

55:15

💬 Q&Aセッションのまとめ

ウェビナーの最後に行われたQ&Aセッションのまとめです。具体的には、参加者からの質問に対する回答を紹介し、CMOとのスケジュール調整、リリーステスト、独自の容器やバッグの提供などに関する具体的な質問と回答を含んでいます。また、今後のウェビナー改善のためのフィードバックの収集についても触れています。

Keywords

💡バイオロジカル

バイオロジカルは生物由来の医薬品を指し、体内で特定の機能を果たすことができる大分子化合物を含んでいます。このビデオでは、バイオロジカルの供給チェーンの最適化が議論されており、特に臨床試験から診療所への供給について焦点が当てられています。

💡供給チェーン

供給チェーンとは、原材料の調達から最終製品の配送までを網羅する一連のプロセスを指します。ビデオでは、バイオロジカルの供給チェーンに特有の課題とその解決策について詳述されています。

💡臨床試験

臨床試験は、新薬の安全性や有効性を評価するために患者に薬剤を投与する試験です。ビデオでは、バイオロジカルの臨床試験における供給チェーンの重要性が強調されています。

💡CMO（Contract Manufacturing Organization）

CMOとは、契約製造組織の略で、他の企業のために医薬品の製造を行ったり、関連サービスを提供する企業です。ビデオでは、CMOがバイオロジカルの製造と供給チェーンにどのように関与するかが説明されています。

💡プライマリパッケージング

プライマリパッケージングとは、製品を直接保護する包装のことであり、ビデオでは、バイオロジカルの製造後に行われ、製品の品質と安全性を確保する重要なプロセスとして触れられています。

💡セカンダリーパッケージング

セカンダリーパッケージングは、プライマリパッケージングの外側に配置される包装で、運搬や販売の際に製品をさらに保護します。ビデオでは、バイオロジカルのセカンダリーパッケージングの重要性とそれに付随する諸問題が議論されています。

💡冷链管理

冷链管理とは、製品が製造から配送までの間、特定の温度条件下で保管されることを保証するプロセスです。ビデオでは、バイオロジカルの保管と配送において冷链管理の重要性が強調されています。

💡比較剤

比較剤とは、臨床試験で新しい治療法と比較するために使用される既存の治療法のことです。ビデオでは、比較剤の供給とそれに関連するコストと課題について触れられています。

💡IRT（Interactive Response Technology）

IRTとは、インタラクティブレスポンス技術の略で、臨床試験で患者への薬剤の配布を管理するためのシステムです。ビデオでは、IRTシステムの導入とそれに伴う時間とコストの要件が議論されています。

💡QP（Qualified Person）

QPとは、適正な人物のことで、EUにおいて医薬品がGMP基準に従って加工されたことを保証する役割を持ちます。ビデオでは、QPがバイオロジカルのEUへの輸入とリリースプロセスにどのように関与するかが説明されています。

Highlights

今日的X Talks网络研讨会主题为“生物制剂从配方到临床的最佳供应链映射”，由Sumaya主持。

研讨会将包括与演讲者的问答环节，鼓励参与者通过聊天框提交问题和评论。

Sharp Clinical作为UDG Healthcare的一部分，为制药和生物技术客户提供包装和供应链服务。

Sasha Sonenberg作为Sharp Clinical全球业务发展负责人，支持临床试验市场的增长策略。

Andrea Wagner是Berkshire Sterile Manufacturing的联合创始人，专注于小批量无菌灌装。

网络研讨会旨在互动，最佳参与方式是积极提出问题和评论。

生物制剂在临床试验和商业阶段的增长，以及它们在全球畅销药品中的主导地位。

生物制剂供应链的独特性和对临床供应的影响，例如治疗成本、疾病治疗的个性化以及远程治疗的兴起。

生物制剂供应链面临的挑战，包括复杂性增加、患者招募时间缩短和跨国法规的多样性。

临床试验供应链的规划和准备，以及如何找到合适的服务提供商。

与服务提供商合作的重要性，以及在早期阶段就让他们参与项目。

Berkshire Sterling Manufacturing提供基于隔离器技术的无菌灌装和配方服务。

选择CMO（合同生产组织）时要考虑的因素，包括质量体系、时间线和灵活性。

评估CMO时的策略，包括信息请求、提案请求和报价收集。

确保与CMO的兼容性，包括质量保证和项目协调的重要性。

在CMO选择过程中，沟通的重要性以及如何建立有效的沟通流程。

在CMO执行阶段，如何确保生产过程的顺利进行和质量控制。

在与CMO合作时，如何管理期望并确保双方目标一致。

在临床试验供应链中，如何考虑和规划产品的存储和分发。

网络研讨会的问答环节，解答参与者关于CMO选择、合作和临床试验供应链的问题。

Transcripts

well good day to everyone joining us and

welcome to today's x talks webinar

today's talk is entitled mapping the

optimal supply chain for biologics from

formulation to clinic my name is sumaya

and i'll be your ex talks moderator for

today

today's webinar will live on for

approximately 60 minutes this

presentation includes a q a session with

our speakers

this webinar is designed to be

interactive and webinars work best when

you're involved so please feel free to

submit questions and comments for

speakers throughout the presentation

using the questions chat box and will

try to attend to your questions during

the q a session

this chat box is located in the control

panel and that's found on the right hand

side of your screen if you require

assistance please contact me at any time

by sending me a message using that chat

panel

at this time all participants are in

listen only mode please also note that

this event will be recorded and made

available for future streaming on

xtalks.com

at this point i'd like to thank sharp

clinical who developed the content for

this presentation

sharp part of udg healthcare is a global

leader in contract pharmaceutical

packaging and advanced clinical supply

chain services offering solutions and

support to pharma and biotech clients

from phase one trials all the way

through to rapid launch and

commercialization

the organization has state of the art

facilities in the united states united

kingdom belgium and the netherlands and

over 32 clinical depots globally

covering every region of the world

now it's my pleasure to introduce our

speakers for today's event and our first

speaker is sasha sonenberg sasha

sonnenberg joined sharp clinical in

september 2019 as global head of

business development supporting sharp

strategy for growth in the clinical

trial market

before joining sharp he held management

positions at market and fable farmer

services overseeing global operations

and business development activities

sonenberg is an active member of the isp

community of practice on investigational

products where he's a co-author of the

good practice guide for booklet labels

in clinical trials and currently leads a

tax task team developing a good practice

guide on patient-centric logistics

direct-to-patient services

and our second speaker is andrea wagner

dr andrea wagner is a co-founder of

berkshire sterile manufacturing she

successfully grew the company to an

industry leader in small batch sterile

fill finish by effectively developing

unique isolator-based flexible fillers

to fulfill an unanswered demand in the

market

her role today involves closely

monitoring the coordination of

engineering quality manufacturing and

project management teams to meet the

constantly changing customer

requirements and critical deadlines

managing sales and client relationships

and affecting affecting pivotal

decisions the growth of the company to

meet market needs

so now without further ado i'll pass

control to our first speaker and that's

sasha's

whenever you're ready you can go ahead

and get started

okay um thanks um shumaya for the very

kind introduction and um warm up for

today's webinar

i hope that everybody can see my screen

um and we will go to the first couple of

slides before i hand over to andrea and

then

um you have the pleasure to to welcome

you back for the remaining slides

um yeah talking about the optimal supply

chain for your biologics from

formulation to clinic

um

we see more and more biologics coming

into clinical trials and of course also

into commercial stage and before we move

forward

i want to make sure we are

talk looking at what we will cover today

so

we will start with the brief industry

overview i will keep it really short but

just to

bring everybody up to speed where we

stand in regards to biologics and

commercialization we will talk about the

elements of the traditional supply chain

um what to look out for what kind of

challenges you might face and how to

prepare and how to overcome them

and then how to identify the right

partner and what is very important also

to being open to collaborate with your

partner and to engage them at an early

stage

so let's have a look at the

annual global drug sales

when you look here at the graph on the

left

you see

the development of

drug sales between 2016 and up to 2024

we see that biotech products um

increase as well as other pharma

products but what is important here is

that in terms of

um value

the biologic drugs are having a

dominating

position among global blockbusters

uh we know that 15

of the top selling prescription drugs in

2018 or 10 of them were biologics and

overall 35

53 of the top 100 selling prescription

and otc products in 2018 were biotech

products

some of them are named here so we see

that there is a huge market and

what is important also when we look here

to the next slide

is i'm looking at the biologics value

chain and

what is making the biologic supply chain

so unique

and

how it is impacting also clinical

supplies what you see here on the table

is on the left the traditional medicine

small molecule drug supply chain and i

will not go into the details here in the

middle we have the modern biologics and

on the right what has started and seen a

huge development over the last three to

five years the cell and gene therapy

market but we will focus today

on the modern biologic supply chain

um we saw already on the previous slide

that from the value perspective the

biologics are on top of the

of the graphs and um in a leading

position and this is because that

the therapy on an annual basis on

average costs hundred thousand or even

more it's used mainly for chronic

diseases

personalized um general remote

treatments are coming and

um

it is something where

when you go into the development um

and you do um

you have the product it's more

difficult to handle in general this is

because we are dealing here very often

with living organisms with cells

what we see as well is that

the volumes in general are going down on

the other side the number of batch um

processes or manufactured batches

actually

increasing

and

because of the nature of the product

we see a lot of requirements from a cold

chain perspective which is making the

global distribution especially at the

stage of the clinical trial and also the

warehousing more challenging as you need

to maintain strict temperature

requirements i need to establish

and sometimes qualify validate solutions

from packaging shipping

and distribution to the site um and

there are also a lot of

track and trace technologies that

potentially can be used in order to make

your life easier and to gain real-time

access to the data of the drug that you

are distributing

if you look to some of the challenges

that we

see

currently

we realize that

protocols are becoming more complex and

this is also something when we look to

the current situation

where we are in a um pandemic situation

course because of covet 19

there are discussions if it is a chance

to simplify things or

if protocols might become more complex

um and um at the moment in order to

mitigate risks um what i see is that

protocols are actually becoming more

complex uh lead times to enroll patients

are becoming shorter

um you have a lot of different countries

specific regulations when it comes for

the um about the or to the import

of product

dealing with multiple languages um with

again the the regulations that come

along with the different countries

getting approval

um to to use your label text

very often with these kind of new drugs

there's a lack of experience because

there's no real historical data

um the cold shame management also we

have seen um a fast and and really

pleasing development in terms of

um technical solution when it comes to

to shippers and loggers

we still see issues in this area and

especially

um with the global

vaccine distribution potentially

absorbing a lot of coal chain capacity

um there is a certain challenge there as

well moving forward um general logistics

um not just because of the the situation

we face with covet

but um

logistics there can always be

interruptions and with the sensitive

product

such as the biologics this can always be

a challenge

and another challenge is of course also

cross-vendor management

having multiple vendors involved because

you might not

find one that can provide all services

managing all of them assuring the

communication across them

is working well

is something that can be a challenge and

can consume a lot of your time and of

your budget

so looking into

the clinical trial supply road and it is

a road that can be a very smooth road

but it can also be a very bumpy road and

i think the the key takeaways for today

that we want to um

share with you here and hopefully have

as an outcome of today's webinar

is

what you need to do in order to to plan

to find your right service provider and

to make the road as smooth and um

not as curvy as this one but straight

and and make it an easy ride

um so we will go through the different

stages uh planning and preparation um

analytical and formulation manufacturing

and primary packaging where i will hand

over soon to andrea and i will then

cover again the secondary packaging part

going looking more detailed into storage

and distribution and execution and

review

and with that i will hand over to andrea

who will now take the bsm part

thank you sasha for the kind

introduction

um just so folks know um berkshire

sterling manufacturing is a drug

production

company

we are a fill finish company that

provides sterile filling and formulation

using isolator based technology and

flexible fillers and by flexible fillers

we can fill syringes vials and

cartridges

so

i'm going to be speaking about the drug

product production side of the business

and some of the takeaways here

are

how to find the best cmo the typical

timing required and what you can do as a

sponsor of a cmo to

have a smooth transition once you've

found your perfect match for your cmo

so let's talk a little bit about the

drug product

process and how it works

so let's pretend

that you're trying to find the right

life partner

and when doing so you might ask

questions such as what are your

interests how do you like your coffee

what do you where do you like to go to

dinner

these are things that you're trying to

get to know the other party and

determine whether this would be a great

fit for the long term

well in a cmo you need to do the same

thing

you need to look at you need to ask a

lot of questions and you need to know

what questions to ask and so we're going

to give you those tools

and then once you find

that perfect fit

you're going to evaluate the cmo with a

request for information a request for

proposal

and you're going to collect those quotes

and then you're going to pick your cmo

but there's a little bit more involved

there

and we're going to give you some tools

in which to uncover

the best

partner so that you can find your

perfect match

but prior to making that choice you

should understand this process and

gather the data that's required and

provide the correct timing

so but before going on

we'd like to

do a poll question

and this question is what are your

greatest concerns when looking for fill

finish cmo

thank you andrea so

audience members you should be seeing

that poll question on your screens so

like andrea mentioned that question is

what what is your greatest concern when

looking for full finished cmo and your

options are as follows the quality

system stability assurance or that's

meeting your tight timeline or that's

container flexibility or that could be

cost or it's other so you can go ahead

and vote on that poll just by clicking

on the option that suits you best

and once again that question is what is

your greatest concern when looking for a

full finished cmo

okay i'll give you a couple more seconds

to answer that i see that

we're almost there majority of audience

numbers are almost voting perfect so

let's go ahead and close the poll

and the results are as follows

okay so you should be seeing the results

on your screens

and so the majority of votes went to the

quality system stability assurance which

was at 56 percent followed by meeting

your tight timeline at 33

and then cost at seven percent other at

four percent and lastly no votes went to

container flexibility

so back to you andrea i'll send back

control to you

all right thank you so much

thank you so much so

the quality systems and sterility

assurance number one not surprising

um meaning your timeline number two

um

all right so going back to our perfect

match you're looking for the right cmo

and how do you do that how do you get

there so we're going to help you with

that

as a cmo the questions that are posed to

us are typically listed here

when you're looking for a cmo you should

consider what you need so for example do

you need an immediate need timing is

that important to you

what do you need the next two years so

the relationship here that you're

choosing is a long-term relationship

it's typically not a short term

so ideally you want the cmo to take you

at least two years out

and you need to look at their quality

and

what the timing is again and things like

analytical testing do you need that

transferred formulation is it difficult

or is it easy

label kidding distribution do you is

your cmo have those attributes do they

have a partner like sharp that can

perform that for you these are the types

of questions that

you might want to be asking

and the cmo the contract manufacturing

organization

is likely to ask you a lot of questions

so they might ask you things like your

timing because their calendar may be

full for nine months and you may need it

in three months

what is your lot size so your lot size

meaning how many bios fringes or

cartridges you might like to produce in

one given lot

if you're looking to do say 50 000 and

the cmo you're talking to can only do 20

000 that might be a problem for you you

might not be able to cut that down

the toxicity of the active

pharmaceutical ingredient this is a

really important one a lot of people

kind of breeze over that so a lot of

cmos have certain requirements for

certain types of products and that

should be a question um right up front

do you handle

a dea classified substance do you handle

a toxicity of greater than three or

cytotoxic product if you should have one

and maybe that's important from you for

you as well if you don't have a

cytotoxic product you want to

manufacture in a facility that handles

those types of products so those are

considerations how is your formulation

done

is it easy or does it require three days

of complex manipulations

other things like filling is your

product light sensitive oxygen sensitive

temperature sensitive can we accommodate

for those in what phase are you at are

you in a phase one uh trial or are you

going into commercial are you in phase

three do you need uh future capacity uh

very quickly so these are things that

you can consider as you're starting to

develop that list

and in finding the best fit both parties

must be compatible so it's not a

situation of oh i found the best fit but

the cmo is not compatible with you

meaning if you're getting

information back that doesn't seem like

it's going to fit that's an important

aspect to consider

speak to the internal people such as the

process engineering group

the quality control group the quality

assurance group and the manufacturing if

timing is tight make sure to speak with

the materials folks and the planner

to get accurate information about that

and finally qa quality assurance is the

backbone of the decision as we've um

identified here during the poll they

must be able to work together so if

there's personality issues between the

quality groups that is going to be a big

problem later on so that needs to be

resolved up front and should be a high

criteria

so

let's talk about

the struggles in finding the right cmo

so in understanding the drug product

production process is going to help you

create that list of questions that you

can then tackle with your potential cmos

so let's map it out will enable you to

get a better understanding of the

process important aspects you need to

determine the container so if you're

looking to fill vials

and i'm sorry if you're looking to fill

syringes and your cmo only does vials

then that's going to be a problem

qc testing transfer how rugged does that

need to be does it need to happen are

you doing your pc elsewhere does the cmo

require you to do certain things

internally these are things that you

need to ask about formulation again easy

or complex and how much experience do

they have if it is complex and by the

way on the materials

the

equipment required for more complex

formulations most cmos don't have um

multi-use containers anymore so this is

something you should consider as well

sterilizing method do you need sterile

filtration along along with steam

sterilization is everything aseptic if

you're terminally sterilizing and you

don't need a septic

control around your production then you

shouldn't be paying for it

and you're probably at the wrong cmo

filling needs what type of fillers

do you require i noticed that nobody

looked at flexibility and filling but

some people want may want to start in a

vial and go to a syringe does your cmo

have the capability to change over

all right so now let's look at the

approach

so when you're looking at a cmo there's

three stages on the drug product

production side

um so there's a planning and preparation

then you have a really quick execution

stage and then finally you have a

release stage

so

uh let's look at the different groups

involved so there's five critical groups

process engineering quality control

materials group

qa and manufacturing these are all

headed up by one person the coach which

is the project manager

some cmos may have project manager that

can

speak for all of these groups

however i think it is important to be

able to get in touch with the sme in

inside of each of these groups so that

might be a question that you might ask

when you're doing your evaluation

on the planning and prep side so let's

break this out

so here we are at the plane prep that

could take a bit of time and let's talk

about what each of these group members

do so the process engineering group is

going to take your formulation and

they're going to transfer that

information into documents they might do

studies for you they're going to write

your batch record

in

collaboration with all of these other

groups

but that is their role in

transferring your

product in for production

on the quality control side the qc side

they're going to be looking at doing

method transfers if you have a validated

method or qualification if you do not

um they're going to perform your in

process and final release testing

they're also going to be in charge of

releasing the materials and the

chemicals that go into your

product as well as the containers so

these are important people to get to

know

on the materials group they're going to

be ordering everything

for your production and they're going to

assist with the material specs

and they're going to assist with the

release and the kidding of data from of

that material and we call

at berkshire sterile anyway we call that

a piece of paper the bill of materials

the bomb

so their role is pretty important as

well

and then on the quality assurance side

this is again the backbone of the

organization and they're going to be

reviewing all the records and they're

going to be signing off they're the last

sign off on everything so

being able to make sure that they can do

sufficient review and work with your

team as well because you're going to be

signing off too

now we go to the execution as i stated

before this is the quick phase usually

it lasts about a week

the teams involved again are the four

process engineering manufacturing

quality control and quality assurance

your project manager manager will be

leading you through so the process

engineers will assist in the formulation

at least to start with until it becomes

a normal process meaning usually it

takes uh two to three times before

manufacturing takes over but they're

always there in the background

doing being the coach the overseer of it

on the manufacturing side

there's four groups so there's a

component prep group a formulation group

a filth finish group and then an

inspection group

and they're they're basically the worker

bees in terms of making sure that your

product is formulated correctly it's

documented it's filled appropriately

and by the way i should have mentioned

that some of the all the video that

you're seeing here is in-house the

berkshire sterile

and um it's filled correctly and then

it's inspected

on the

quality control side

they'll be in charge during the

execution phase of your in-process

really

testing so and i highly recommend that

you make this in process testing as easy

as possible so a ph test is ideal

or a uv analysis once you get into doing

hplc analysis it can be a little bit

tricky and it can delay a fill if

there's an issue

uh with the standardization prior to

running the test so we encourage um

simple is better during that period of

time and then quality assurance they

really need to be on the floor

so they need to be checking to make sure

the records are being filled out at the

time of um

at the time that the work is being

performed

they need to be available to ensure that

if there's any issue that they can

escalate that

their role is very very important at

this stage as well

now we go on to the release

now we notice we drop that off one of

our team members process engineers

we have a review and release process

that usually lasts four to six weeks

after

the production is completed

in manufacturing they're going to be

doing the inspection it should be a 100

inspection

sometimes this is automated most of the

time it's not

so that is an important aspect the

quality control group is going to be

doing

the release testing and issuing the c of

a the certificate of analysis

and the equality assurance group is

going to be reviewing all of the records

and closing out any discrepancies

related to the production

and then issuing a cfc which is a

certificate of compliance so those are

all of the team members

involved in the production of

the

drug product

now once that's completed then it goes

off to at least in our case to our

partner sharp

to be kitted and distributed and off to

the patient now

as mentioned before we need to think

about timing so this will vary from

client to client and cmo to cmo but you

should definitely expect from the date

after the contract is signed

a six-month process to get from the

beginning to the end

a lot of people require more it could be

nine months there's things that can get

in the way of this like materials

reference standards long lead times

should be considered api

so you should think very carefully about

that now if you're starting now you

might be sitting there thinking oh my

god i have to have my production done in

four months so timing is going to be

much more critical for you than um some

of the other aspects that we've

mentioned or at least as critical as

some of the other aspects that we've

mentioned so starting early is really

important in this process

and we als and this is often the group

that's thought about last so

now how can you make it once you find

that perfect match you're going to be

with the cmo for a while um it could be

two years it could be ten so please uh

consider that how can you make it a

smooth transition to the cmo

what can you do

so

in real estate they talk about location

location location

and the cmo industry we talk about

communication communication

communication so in any good

relationship communication is key

and

in the

dp process that i've just outlined here

it's important to understand that you

might have many members of your team

talking to many members of the other

team

so setting up a successful communication

process is important the project manager

really should be the

person that holds all communication or

at least copies of communication so and

putting in writing especially if it's

important like your

specifications which you own as the drug

sponsor is really critical to ensuring

that you have successful transfer

okay let's go over some things that you

should do

so before you sign up for that contract

you want to review

the technical

quality and timing aspects and make sure

all of your questions are addressed

okay

and the contract itself could be a

longer process as well depending on the

legal ease of the organization that

you're dealing with

you want to ask as many questions as

possible and you want to feel

comfortable with all of those questions

now you know some of the questions to

ask too so during stage one the planning

and prep

you want to make sure that your

formulation is robust

so and your methods so if you have

development that needs to be done

and you want the cmo to do that you need

to communicate that to them so they

don't put it into their planning process

and run into roadblocks which further

delays you in the future

you want to make sure that you provide

thorough details on how you formulate

this right up front before before it's

even quoted this is how it's formulated

if you're going from a 50 mil

beaker to a two liter process or a 1

liter to 100 liter it's a huge step and

you're going to require some

formulation transfer

and some studies to be able to

transition that up and you may do that

internally or you may do that at the cmo

again something you need to convey to

them

make sure that the specifications can be

met

don't transfer specifications to the cmo

or ask the cmo what the specifications

for your product should be because they

don't know

but make sure that you know that they

can be met

and with confidence

and give a quick thorough review of all

the quality documents you own them as

much as the cmo does the cmo owns them

you own them they're part of your

process going forward they will be

inspected by regulators it is important

that you give them enough time for

review

and avoid last-minute changes

this is the death of all um

products in my opinion when

clients or cmos come in and say oh we

need to make this change the minute

before it starts try and avoid that

now on the execution stage what can you

do you can get the batch record approved

i say a few days i would like a few

weeks

prior to the fill date to prevent

deviations if people can

prepare properly you're going to get

less deviations on the actual run

have the engineers in the formulation

ensure that they're properly training

the manufacturing group be part of that

process

you

you are the owner of this production

they you need to make sure that the

information is being conveyed not only

in written form but also in verbal form

to the people that are going to be

handling your production

and then be available finally

if your fill goes into midnight 1am in

the morning

you're gonna have to stay up late to be

part of that in these times of covid uh

they should have remote um viewing

available to you and you should be

available if they need to get in touch

with you in case there's an issue this

is

critically important

all right so in review

finding the right cmo the perfect fit

we went over the timing and the

expectations and what you could do to

ensure that the transfer once you do

find that perfect fit goes seamlessly

because we don't want to be in a

situation where like most of us require

contractors and we really don't like

them after

they get our job done so we want to like

our cmo at the end and this is what we

can all do to work better together

now i would like to

switch it back over to sharp and they

can talk to you about what you do after

you get your drug product produced and

it goes to them

thank you very much andrea for

the

good overview and how you manage the the

production and filling part

um i hope the transition to my

presentation or back to my presentation

went well

yep we can see that

okay perfect

as andrea mentioned um i think uh

element or the one of the most critical

element is communication um and managing

expectations and understanding um the

situation the cmo but also the client is

in

so

i think asking questions is a very

important part to make sure that you get

a good understanding about the

requirements capabilities

and you see here a couple of examples

that we typically

receive there of course many many more

and i will not go through the details

here but um

some of the i think important questions

are

um is of course inspection about

regulatory agencies um how flexible are

you and can you meet our timelines and

demands and i always like this question

because to me it always comes back um

with another question is okay we need to

have information that are usually not

available then and so it's really about

communicating and being open

um andrea mentioned the part um having

people in the plant um not face to face

maybe at the moment to observe

manufacturing but have you set up

virtual capacity or capabilities um what

kind of technologies do you have to

support the primary secondary packaging

the labeling

can you do this under different

temperature conditions for example

audit and quality

specific questions obviously and in the

times of the pandemic also do you have

the

capabilities to perform a virtual audits

how can we read your documents do you

have a virtual side tour um these are

all questions that we receive

and um

over the last couple of months of course

also

how do you

or how are you prepared to mitigate the

brexit impact

do you have

[Music]

distribution or packaging capacities

within the eu

and on the other side of course

what are actions in place to mitigate

the impact of covet 19 so that your

packaging run but also the distribution

of the material to the clinic or to the

patient is not in danger

on the other side

the cmo might have a lot of questions as

well

and

we are always

asked by our colleagues in project

management and productionists at a very

early stage

to request an sds to classify the

material to see if we can handle it and

on the other side we know that this kind

of information is not always available

what kind of blinding strategy do you

have is it an open label study or is it

a blinded maybe even double-blinded

study

timelines again yeah when is your first

patient in date is always a very good

indicator and

sometimes it is or might even be a

challenge when you look at the first

patient in date and then you see it's

only four weeks away and you have to

perform a full packaging distribution

exercise

volumes how many campaigns do you run

what kind of services are overall

required are there any special

requirements um

not necessarily child resistant senior

friendly but

maybe in the post covert world we will

see more adherence packaging which will

add complexity

we'll talk about labeling

sometimes it looks like a simple sticker

but there are many uh requirements um

related to materials and of course to

the text

that you put on the label

when we talk about biologics um the

temperature is a very critical element

usually we have temperature

requirements around two to eight but

they can always be also be in the

negative environment

um so identifying

the right solution for uh packaging

needs to be under certain conditions in

case you have limited stability data

and what kind of solution and also

service partner you use for the

distribution are critical here

and then which countries are

included in your study

very important because it will have a

huge impact on the timeline not

necessarily from the shipping but

obtaining

required documents

is a very critical point and

understanding really how long does it

take

and um

i hope you don't have too many people

from clinical operations but i've seen

it in the past very often and oh yeah we

add another country we can start

distribution tomorrow this is usually

not how it works and there is a lot of

preparation you might want to look into

mapping out the distribution

channel and again you need to obtain

import licenses permits and that might

in some cases take a couple of weeks

something that is important to look at

at an early stage is

do you require for your study an irt

system an interactive response

technology to manage the allocation of

drug to the patient do you

require randomization

um

do you already have a clear idea do you

have experience in the iit field

um or do you have some groups dedicated

groups that are working with this

on this topic

um i've seen that very often companies

starting here again and again

because people are moving that have

maybe previously worked with iot systems

moved into your roles or to new

companies so

talk to your vendor

ask them for their

support

and for their

advice they usually have a lot of

experience

and

looking to a timeline setting up an iot

system depending on the complexity of

the study can easily take six to eight

weeks so if you don't want to be under

extreme pressure you might

want to add another two to four weeks

just to be on the safe side if you have

a less complex study maybe you don't

need to full-blown irt but you still

want to have full visibility on your

inventory that you have at the sides so

an inventory management system might be

a less complex solution but it still can

help you to

initiate supplies to to look at

your overall drug

stock

and to initiate

shipments another topic that um

very often before

you um

look into executing the the filling and

packaging

um

asks tasks you're looking at is the

whole area of comparator sourcing

um with biologics comparative sourcing

has reached a new uh financial dimension

and it can have a huge and significant

impact on your study budget

looking into comparators

it is important to to understand of

course what kind of material you're

looking for but also what you are

willing to share because

depending from where you source or what

kind of comparative product you are

looking at if you do not disclose the

study material details it will be

difficult or more challenging to obtain

the required drug and specific documents

to support for example the disability

data

in which regions do you need to require

the supplies to be again which countries

are involved

a very important point when we talk

about comparator sourcing when we talk

about biles

especially pre-filled syringes is around

the whole

blinding topic

are you able to get the exact material

what is your blinding strategy

um so there are a lot of things and

if you

involve your partner at an early stage

we can say that based on experience uh

if we have the time to look into the

market we can look like in the example

that you see here here at the button we

can research if a certain drug is

available in a different market we can

provide information around it and this

can lead to a significant price

decrease which given the the

drug price of some of the biological

products can again have a significant

savings impact on your budget

so when we receive the material from bsm

usually

our next step

is um the secondary packaging

we would of course then execute but

before you execute there are so many

other things that you need to to look at

you need to look at how to best protect

protect your product what are the

requirements do you need not just shock

protection but maybe also protection

from

light from humidity maybe even during

the the packaging project

uh what kind of components need to be

included in

a drug kit is it the truck itself are

there any other

um ancillary supplies for example any

kind of documentation

um

something that i learned in the past and

it was confirmed by colleagues when

talking about this and preparing the

presentation is

very often people design kits

without

thinking about the next step

and i have seen

kids where

in the initial discussion um they were

supposed to be

10 to 20 centimeter long

um so a specific packaging solution for

cold chain distribution was offered but

when the actual

kids arrived at the distribution company

the kids were much larger

and they had to use instead of a 24

liter coal chain shipper a 96 liter for

one kit and this had a significant price

where

the

costs went up for one shipment from

approximately five to six hundred

dollars to over three thousand

so be very careful when you

design

your kids and also think about the

patient that

he has to handle she has to handle it

and you don't want to make it too

difficult

um

any specific materials that are required

are there regulatory

implications that you need to consider

any other

secondary packaging solution that you

you need to think of it's a very very

complex topic and the the next part is

labeling and

very often people say oh yeah we need to

put the sticker

on the drug just to comply with the

regulatory requirements

but um the term labeling strategy is not

coming from

from nowhere there is a lot of thoughts

behind um what kind of material do you

need to have a specific clue especially

when you talk about

temperature or cold chain conditions

especially when you go into

negative temperature conditions

if you have a plastic container you need

to look

is there potential risk that the glue

might mitigate through the material um

which is for example something when you

look at eye drops this can be very um

dangerous

um

then something that has a sick or can

have a significant impact on the

timeline

is the whole topic about translation and

regulatory approval i have seen here

turnaround times from a couple of weeks

but also to more than a year so having a

clear approach

and knowing

what you need to have on the label is

really critical

i will move a little bit faster because

some of the time

if you are going into different regions

for example the eu

um you are facing the topic of the

qualified person

and

as very often the question okay is this

something i need

larger companies might have set up this

process but if you're working for a

smaller um company or virtual company

and you're running your first trial

you might ask yourself what is a

qualified person what is he actually

doing and this is a specific role that

is existing within the eu

that guarantees that any material that

is coming into the eu

has been processed according cgmp

or eu gmp guidelines

and also if a manufacturing step is

performed um

in the eu that the material is then

released by the qp before it is shipped

to the site

um

overall qps are

i think

a benefit as they help to improve

quality

but what is important to understand here

that before a qp could import or release

material they might actually ask for a

supply chain audit

and this what does it mean

usually you look into the last step of

the supply chain from a manufacturing or

packaging perspective before the

material came into the eu you might need

to look into labs that um

performed an analysis

of the material that that is used in the

pla in the trial

um and

this is something that can take a lot of

time it's not just the availability of

the qp but you need to agree on an audit

appointment so the

potential manufacturing side outside of

the eu the lab they need to be available

and then it needs to be as an audit

report that needs to be written

um you need to give time to provide an

audit response so there are a lot of

impacts from a timing perspective

storage and distribution

this is

a really complex topic

they can

change of course from

a country by country perspective

but when we talk about distribution is

of course do you need the depot where

and how many um the how many has an

impact on how many um stock do you need

because every depot will increase also

your overage

so usually going with the smaller number

of depots unless there is a regulatory

requirement

such as in brazil for example

or argentina where it makes sense to

have a depot you can try to to limit the

number of depots to central ones and

then to distribute globally um we

mentioned earlier the topic of an import

license what kind of packaging

monitoring solution to choose

um code chain requirements um a lot of

different things but i've seen also very

often that the question is asked do you

need to return a destruction service and

um the answer is no and at the later

stage in the study the

request is coming oh the sites cannot

handle this can you please also offer

return and destruction service and at a

later stage this can cause some problems

of

re-exporting drugs

from a certain country so it's always

good to include this as an early stage

in the discussion

so we see that there is a lot of complex

supply chain and

going briefly over this topic that can

easily fill an entire day of discussion

we hope that moving forward you can

simplify it

recommendations

really from our side is

understanding each other's expectations

don't just assume something ask

questions share information don't think

that the other party already knows about

it

communicate early and often and get your

partner involved

you can just benefit from their

experience

they can help with study plan and design

they can share their experience and help

you to smooth the road and to have a

soft ride while you develop your

clinical supply chain

and with that i

um

hand it over back to shamaya for the

question and answer session

fantastic thank you sasha and andrew for

that very interesting and detailed

presentation so that does bring us to

our q a portion audience members so you

can still send in questions to sasha and

andrew right now using that chat box

we did receive some questions already so

i'll start off with the first question

and that question is

does a client have to determine material

materials to be used so stoppers vials

caps etc or will the cmo make

recommendations

so that question would be for me um so

both are correct so the client does need

to ultimately choose however the cmo

does often make recommendations for what

they currently have in stock or they've

used in the past for the change parts so

eliminating that lead time

great thank you andrea and our next

question is

can i use a contract lab for release

testing instead of the cmos laboratory

okay um yes that is a yes some cmos have

a restrictions on that so you should

check uh with your cmo but that

definitely can be done and has been done

fantastic and another question from an

audience member and that question is can

berkshire sterile manufacturing prefer

unique containers or bags

again that would be a yes

we currently do syringes vials and

cartridges we've done some specialty

containers as well

and we have done some bag filling too

all right interesting and we have

another interesting question from an

audience member and that question is how

quickly can a new client get on a cmo's

fill schedule

so most cmos book out six to nine months

so that's what you should be prepared to

listen to or hear but what i recommend

is to contract with them and get on

their wait list so if there's a

cancellation and many times there are

especially if uh it's a clinical phase

cmo

you can slip into that spot that becomes

available

fantastic and

our

another question from an audience number

that question is does bsm allow clients

to watch their formulation and fill

or has this changed has this changed as

a result of

covid19 yeah so uh berkshire sterile has

cameras set up in all of the clean rooms

so you can watch remotely and we've

expanded that technology since covet 19.

and we encourage and almost insist that

clients be a part of that process

okay great another question from an

audience member and that question is do

you provide formulation free freeze

dryers

so we do have lyophilization

capabilities here at berkshire sterile

we're um doing an expansion which will

expand that so currently we offer

clinical

and in 2022 beginning of 2022 we'll have

commercial

capacity for that in terms of about 30

000 10r files

great thank you andrea another question

from an audience member

do you do in-house sterility testing

so we currently outsource for berkshire

sterile we currently outsource uh to sgs

however we will be bringing that

in-house next year with a sterility

isolator from fedegari

great thank you andrew we're getting

lots of interesting questions just

making sure that i'm getting to all of

them but it seems like that's all we

have for today so thank you very much

for all those answers andrea and um

everyone for sending in those questions

as well we reached the end of the q a

portion of this webinar if you couldn't

attend to your questions

the team at sharp clinical and berkshire

may follow up with you after this

presentation as well so if you have

further

questions or comments you can direct

them to the contact information showing

on your screens right now so go ahead

quickly drop them down

i just wanted to thank everyone again

for participating in today's webinar and

you will be receiving a follow-up email

from xbox with access to the recorded

archive for this event a server window

will be popping up on your screen your

participation is appreciated as it will

help us improve our future webinars now

i'm about to send you a link in your

chat box you'll be able to view the

recording of this event at that link and

also share the link with your colleagues

when they register for the recording as

well now please join us in thanking

sasha sonenberg and andrea wagner for

that fantastic presentation on behalf of

the team at x talks we thank you for

joining us take care bye for now

you