Drugs

CDER Drug Inspection Common Deficiencies

CDER Office of Process and Facilities branch chief Ying Zhang recently presented (see slides) common issues and deficiencies cited during pre‐approval drug inspections. Speaking at the Pharma and Biopharma Outsourcing Association’s annual conference in Rockville, MD 9/20, Zhang listed the deficiencies and they include:

Inconsistencies between facility information in 356h form and Common Technical Document Modules S.2 and P.3
Inconsistencies in reported Facility Establishment Identifier or headquarters site provided
Missing contract facilities used for submission batches (list in Module 3)
Missing drug substance manufacturing testing facilities listed in drug master file
Specify if only sourcing from specific facilities
Lack of detailed information regarding operations or tests to be conducted at each facility
Facility not performing listed function or unaware it was referenced in the ANDA
Facility no longer in commercial operation

Zhang also noted another troubling deficiency cited in preapproval inspections, which is a “lack of conformance to application and data integrity issues.” For example, she said, this includes falsified data (complete fabrication of sterility testing, environmental monitoring, water for injection testing, biological indicators for sterilization, bioburden samples, endotoxin testing, and media fills). Other concerns involve quality assurance unit approval of incomplete or erroneous laboratory data, changes of specification (widening) not reported in the application, and testing into compliance, she said.

Additionally, Zhang pointed out common issues and deficiencies observed during contract facility inspections. These include:

Equipment not adequately qualified, maintained and upgraded
Inadequate process validation
Inadequate method transfer
Inadequate operation instructions in batch record
Process deviations are not thoroughly investigated; lack of implementation of appropriate CAPA.
Lack of appropriate change control
Lack of appropriate communication with applicant: such as the knowledge transfer from applicant to contract facility about product and process development information; and contract facilities sharing product quality information

Gupta Raises Concerns About Overton’s Independence, Ideology

FDA commissioner nominee Heidi Overton’s responses on vaccines, contraception and abortion medication during her 9/24 Senate confirmation hearing raise concerns that ideology could influence her decision-making if she takes over the agency, MSNBC senior medical analyst Dr. Vin Gupta said Friday. Gupta was particularly critical of Overton’

Overton Confirmation Remains Uncertain After Senate Hearing

FDA commissioner nominee Heidi Overton emerged from her Senate confirmation hearing Thursday (see earlier story) without resolving questions about whether she has enough Republican support to advance — and with a rapidly narrowing window for confirmation before the midterm elections. The Senate Health, Education, Labor and Pensions Committee hearing provided few

FDA Classifies Boston Scientific Imager II Catheter Recall as Class I

FDA has classified Boston Scientific's recall of its Imager II Angiographic Catheters as Class I because a manufacturing problem could cause catheter tips to degrade and detach, potentially resulting in life-threatening complications. The agency announced the Class I classification 9/25, updating an Early Alert it issued

FDA Approves Gazyva for Childhood-Onset Idiopathic Nephrotic Syndrome

FDA has approved Roche’s Gazyva (obinutuzumab) for reducing the risk of relapse in adults and children aged 2 and older with frequently relapsing or steroid-dependent, childhood-onset idiopathic nephrotic syndrome who are in remission. The expanded approval covers the use of the CD20-directed antibody beyond its existing

Read more

Gupta Raises Concerns About Overton’s Independence, Ideology

Overton Confirmation Remains Uncertain After Senate Hearing

FDA Classifies Boston Scientific Imager II Catheter Recall as Class I

FDA Approves Gazyva for Childhood-Onset Idiopathic Nephrotic Syndrome