BioPharm

6 BioPharm International eBook April 2019 www.biopharminternational.com Outsourcing Resources Chemistry, Manufacturing, and Controls more biopharmaceutical compa- nies, pa r t ic ularly star t-up com- panies, have been using contract deve lopme nt a nd ma nu fac t u r- ing organizations (CDMOs) based on capacity, capability, in-house e x p er t ise, a nd busi ness mo del to bring their biologic drug can- didate from proof-of-concept to patient. DUE DILIGENCE W hy emphasi ze t he c hem ist r y, m a nu f a c t u r i n g , a n d c o nt r o l s (CMC) due diligence process? It is a long, costly, and risky jour ney for a biotech company t o d e v e l o p it s d r u g f r o m d i s - c o v e r y t o c o m m e r c i a l i z a t i o n ( F i g u r e 1). For accelerated d r ug development, biotech companies often prefer to select CDMOs and s e t- up a c l i n ic a l - ph a s e ap pr o - pr iate par tnership to overcome the challenges during the dr ug development. CMC plays a crit- ica l role i n establ ish i ng st rate - gies for accelerated development and identifying gaps as well as in project execution from DNA to invest igat iona l new drug (IND) in less than two years. The CMC due d i l ige nce pro cess e n su res that the drug substance (DS) and drug product (DP) meet the qual- ity, safety, and efficacy standards required by industry and regula- tory agencies for clinical trials and patient treatment. To create a mutually trusted and respectful partnership between CDMO and sponsor, transparency, accountability, and a responsive feedback system are essential. T h e C M C d u e d i l i g e n c e p r o c e s s a l l o w s s p o n s o r s t o i d e nt i f y t h e p o t e nt i a l m a nu - f a c t u r i n g c h a l l e n g e s , a n t i c i - pate a nd re me d iate r isk s, a nd p r o v i d e s o l u t i o n s ( F i g u r e 2) . T he ma nu fac t u r i ng c ha l lenges and r isks are associated w ith a variety of factors, including bio- logical drug molecular complex- ity, process development, scale-up, equipment capabilities, facility fit, manufacturing operation, regula- tory compliance, control strategy, sa fet y, pur it y, qua lit y, ef f icac y, analytical method development, qualification, validation, formu- lation, DS/DP stability, releasing specification setting, and CDMO company culture and their best practices. S e l e c t i o n o f C D M O s i s de p e nd e nt up on mu lt iple fac- tors, such as busi ness cont i nu- it y, m a nu f a c t u r i n g o p e r at io n risk, quality, and regulatory risks ( Fi g u r e 3). T h is business model has been w idely used in accel- e r at e d d r u g d e v e l o p m e nt f o r the 'first-to-market' approach to minimize high failure rate and minimize the large cost invested upf r ont for lab or, e qu ipme nt, Figure 1. Road map for biologic drugs: R&D to commercialization. MTD/MFD is maximally tolerated dose/maximum feasible dose. CMO is contract manufacturing organization. DP is drug product. All fi gures courtesy of the authors.

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