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8 BioPharm International eBook April 2019 www.biopharminternational.com Outsourcing Resources Chemistry, Manufacturing, and Controls Step CDMO evaluation and selection procedure 1 Generate a list (~5 –10) of CDMOs and collect basic information such as capabilit y, capacit y, qualit y. 2 Contact listed CDMOs with questionnaire generated from sponsor. 3 Shor ten the CDMO list (~3–5) based on availabilit y, exper tise, capacit y, location, cost, etc. 4 Execute confidential disclosure agreement (CDA) to obtain additional information. 5 Request for proposal (RFP) from CDMOs (~2–3), followed by proposal review and ser vice price negotiation. 6 Per form on-site technical diligence visit to obtain detailed information to refine proposal and statement of work. 7 Negotiate contract and finalize work statement, qualit y agreement, and legal documents. 8 Schedule kick-of f meeting, which includes cell-line development, process development, manufacturing, project management, and timelines Table I. General procedure from contract development and manufacturing organization (CDMO) evaluation and selection. Call for Peer-Review Papers BioPharm International accepts four types of peer-review papers that are considered: standard data-driven, novel research; topical literature or patent review; technical case studies/technical application notes; and science-based opinion papers. Manuscripts for peer-review papers are accepted on an ongoing basis. Publication priority is given to papers in the order they are accepted for publication. Submitted papers are initially screened by the editors, then submitted for formal review by a member of the editorial advisory board, who will review the article for technical interest and content in a double- blind review process. Article acceptance is conditioned on the reviewer's approval. Once accepted for publication, a paper typically is published within three to five months. Peer-review papers are published in the print and digital editions of BioPharm International, and on www.BioPharmInternational.com. Links to the online versions of peer- review papers also are featured in e-newsletters distributed to the publication's audience. To learn more about the peer-review submission process, click the Submission Guidelines link on www.BioPharmInternational.com. 22 BioPharm International September 2018 www.biopharminternational.com science photo/Shutterstock.com A risk-based approach based on a pharmacological and toxico- logical evaluation is becoming perceived in the industy as a sci- ence-based approach that ensures safety of pharmaceuticals. Since the publication of International Council for Harmonization (ICH) Q9 Quality Risk Management, the application of this approach to the quality management of pharmaceuticals has been considered essential, and its application has also been extended to the cleaning validation of pharmaceutical manufactur- ing equipment. Limits such as 1/100 0, 1/10,000, and 10 ppm were convention- ally used in cleaning validation, but these limits can not be scientif ically justif ied and are arbitrary. In September 2010, the International Society for Pharmaceutical Engineering (ISPE) published a new base- line guide called Risk-Based Manufacture of Pharmaceutical Products (Risk-MaPP). Risk-MaPP provides a scientific and risk- based approach, based on ICH Q9 Quality Risk Management principles, to manage the risk of cross-contamination to achieve and maintain an appropriate balance between product qualit y and operator safet y (1). The basic concept of Risk-MaPP requires a consistent and science-based approach Takashi Kaminagayoshi, is director and head of manufacturing operations; Kosuke Takenaka, Tetsuya Ohta, Tomohiro Doi, and Makoto Sadamitsu are principal scientists; Shunsuke Omori is scientist; and Shinji Tsuji and Yoshiaki Miko are associate directors; all are at Biopharmaceuticals Process and Product Development, Pharmaceutical Sciences, Takeda Pharmaceutical. Osamu Shirokizawa is director and senior consultant, Life Scientia, and Andrew Walsh is president, Center for Pharmaceutical Cleaning Innovation. PEER-REVIEWED Submitted: Dec. 8, 2017 Accepted: Apr. 11, 2018. ABSTRACT Currently, risk management based on a scientific approach is becoming required in the establishment of cleaning validation limits for pharmaceutical manufacturing equipment, as the acceptable daily exposure (ADE), which is set based on pharmacological and toxicological evaluation, is increasingly applied. At the early stage of development, ADE values may be set using the threshold of toxicological concern (TTC) approach due to lack of human data on toxicity. However, TTC values are estimates, so their application requires careful consideration. Especially in biopharmaceuticals (mainly proteins), whether or not the target product item is inactivated and degraded after cleaning is an important issue in evaluating the cleaning process. Therefore, a study was conducted by carrying out "CIP (clean in place) + SIP (steam in place)" and "CI (caustic immersion: alkaline treatment over a certain period of time)", which are usually processes used in the cleaning of antibody drug manufacturing equipment. The inactivation and degradation of antibody drug was evaluated from the molecular structure and physiological activity point of view, using sodium dodecyl sulfate–polyacrylamide gel electrophoresis and surface plasmon resonance. This study was successful in establishing a reliable and effective method for evaluating cleaning processes based on risk. TAKASHI KAMINAGAYOSHI, KOSUKE TAKENAKA, TETSUYA OHTA, TOMOHIRO DOI, SHUNSUKE OMORI, MAKOTO SADAMITSU, SHINJI TSUJI, YOSHIAKI MIKO, OSAMU SHIROKIZAWA, AND ANDREW WALSH Study on an Inactivation Evaluation Method of Cleaning Processes for Biopharmaceuticals Peer-Reviewed location, track-record for deliv- erables, partnership with clients, financial stabilit y, project man- agement, company culture, turn- over rate, and reg ulator y filing experience and support (Table II). L i st i ng t he sp on s or 's e x p e c- t at ion s show s wh at t he fo c u s s h o u l d b e o n , m a i n l y t i m e - l i n e , d e l i v e r a b l e s , c o s t , c o m - m u n i c a t i o n , q u a l i t y (4 , 5 ) , d ispute -resolut ion, i ntel lec t ua l proper t y protection, GMP com- pl ia nc e, a nd r eg u lator y f i l i ng s upp or t . Sp on s or s ne e d to b e aware of potentially dynamic ser- vices provided by CDMOs due to their business nat ure (i.e., rela- tively high turn-over rate) for a long partnership. To c reate a mut ua l ly t r usted a n d r e s p e c t f u l p a r t n e r s h i p b e t w e e n C D M O a n d s p o n s o r, t r a n s p a r e n c y, a c c o u n t a b i l i t y, a nd a responsive feedbac k sys- tem are essential. To maintain a long-ter m hea lt hy a nd produc- t ive re lat ion sh ip, b ot h pa r t ies should put great effort and focus on t i me l i ne s, on-t i me de l ive r- ables, produc t qua lit y, produc t s a fe t y, r eg u l ator y c ompl i a nc e, a nd c om mu n ic at ion e f fe c t ive - ness. One exercise that has been found to maintain a successf ul pa r t ner sh ip is t he use of reg u- lar face-to-face meetings. These m e e t i n g s a l l o w b o t h p a r t i e s to work toget her to ef f ic ient ly

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