BioPharm International - September 2019

BioPharm - Regulatory Sourcebook

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6 BioPharm International eBook September 2019 Regulatory Sourcebook Compliance Report Card months of FDA's fiscal year 2019 (ending September 30). The spike in recalls may be par- tially attributed to the identification of trace nitrosamine contamination in three commonly used medicines during the past year: angiotensin II receptor blockers in 2018, the diabetes treatment pioglitazone in April 2019, and rantidine, a hista- mine-2 blocker in September 2019. Inspections are the primary method regulatory authorities use to identify manufacturing and quality prob- lems. Bet ween 20 09 –2018, FDA inspected, on average, more than 4500 drug and biologics facilities annually. For fiscal year 2019, the number of inspections appear to be down, with only 2733 inspections reported through early August 2019. The number of inspections at domestic drug facilities has declined since 2010; from 2010 –2012, an average of more than 2000 annual inspections were conducted. Only 1325 inspections of US-based drug facilities were reported in 2018. The number of foreign inspections almost doubled from 541 in 2009 to 1005 in 2018; however, fewer than 600 foreign inspections had been conducted through the first 10 months of FDA's fiscal year 2019. Meanwhile, the number of FDA inspections of biologics facilities— both domestic and foreign—has held steady for the past 10 years, and these biologics facilities out- performed drug facilities in inspec- tion results. More than 80% of inspections at biologics facilities resulted in no action indicated (NAI) classification; less than 1% of facilities inspected were classi- fied as official action indicated. For drug facilities, only 47% received an NA I classif ication; a similar number received a voluntary action indicated (VAI) classification. Overall, US-based facilities man- ufac t ur ing dr ugs and biolog ics outperformed foreign facilities. Two- thirds of US facilities received a NAI classification compared with 42% of foreign facilities. More than half of the foreign facilities received a VAI classification; more than 5% were cited for official action indicated. NEW INSPECTIONS AND PROTOCOLS Recog ni zing t he need to sta n- dardize its inspection data col- lection and analysis, FDA, in late 2018, announced a New Inspection Protocol Project (NIPP), that uses standardized electronic inspec- tion protocols to report the data from surveillance and pre-approval inspections (3). S t e r i l e d r u g p r o d u c t s w e r e selected for the first NIPP due to ongoing quality issues with the manufacture of this dr ug t y pe. The agency conducted pilot stud- ies and incorporated feedback to develop protocols to cover critical areas of sterile drug manufacturing and provide data to quickly support quality decisions. Other programs will address non-sterile tablets/cap- sules; bulk powders; transdermal drug delivery; creams, ointments, and solutions; metered dose inhal- ers; terminally sterilized drugs; and active ingredients. ESTABLISHING A QUALITY CULTURE When a drug company is cited for a quality violation, the blame often is directed to the quality team or offending manufacturing, mainte- nance, or analytical unit. A qual- it y c u lt u re shou ld be adopted throughout an organization, said Patrizia Cavazzoni, deputy direc- tor of operations at FDA's Center for Drug Evaluation and Research at the PDA/FDA conference (4). Executive management is ulti- mately responsible for assuring reli- able manufacturing operations and high-quality standards. Inspections reveal a "notable difference: when top management embraces qual- ity," Cavazzoni said. Organizations should plan for and design quality into all systems, invest in manufacturing technolo- gies, guard against decay in opera- tional effectiveness, and ensure suppliers are aligned with your quality practices, she recommended. ABOUT THIS EBOOK U n d e r s t a n d i n g — a n d k e e p i n g informed—about the many regu- lations, compendial requirements, and guidelines present challenges for bio/pharmaceutical companies. In the premiere issue of this BioPharm International Regulatory S o u r c e b o o k , t h e e d it o r s p r e s - ent recent regulatory trends and enforcement actions, a critique of the effectiveness of good manu- fac t ur ing prac tices reg ulations, and insight on biosimilar quality requirements. A focus of this ebook is the first installment of a com- prehensive series on compendial compliance, including a detailed analysis of the impact of pharma- copoeia requirements, challenges with compliance, and why harmo- nization is needed. The ebook also includes links to pertinent guidance documents, contact information for global reg- ulatory authorities, and other tools to aid in compliance. REFERENCES 1. 2019 PDA/FDA Joint Regulatory Conference, Washington, DC, Sept. 16, 2019. 2. FDA, Data Dashboard, https://, accessed Sept. 19, 2019. 3. FDA, "Statement from FDA Commissioner Scott Gottlieb, M.D., on New Steps to Strengthen and Modernize Agency's Oversight and Reporting of Inspections for Sterile Injectable Drugs,", Nov. 9, 2018. 4. P. Cavazzoni, "Advancing Drug Innovation Through Investment in Quality," Presentation, 2019 PDA/FDA Joint Regulatory Conference, Sept. 16, 2019, Washington, DC. BP

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