Regulatory and Quality

Considerations for Contract

Manufacturing

David J. Jaworski Senior Policy Advisor,

Office of Manufacturing and Product Quality, Office of Compliance,

Center for Drug Evaluation and Research FDA/PQRI:

Conference on Evolving Product Quality

North Bethesda, MD

September 17, 2014

Issues of Concern to

Regulators Can the Contract Manufacturing Organization

(CMO) selected perform the work?

Do drug owners only look at cost when selecting a CMO?

Do CMOs and drug owners understand and fulfill their responsibilities?

Are audit programs used by drug owners to evaluate a CMO effective?

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Capability of the CMO

• Do you examine the CMO’s current

performance?

• Do CMOs provide a realistic assessment of their

own capabilities and sources of variability?

• Do the employees have the technical skills and

training to perform the work?

• Does the CMO have suitable equipment that

ensures it will meet your specifications and

CQAs?

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Cost vs Quality • Drug Owner

– Clearly spell out quality

requirements

– Provide incentives for a

CMO to achieve superior

quality

– Provide additional weight

for high quality in decision

making process when

selecting a CMO

– Assure quality as first

priority, not just a financial

decision [full cost of

ownership!]

– Establish and monitor

quality performance

• CMO – Ensure your SOPs align

with customer’s and

Regulations

– Perform your own

assessment of your

customer

– Review the technical

transfer information to

ensure that your

capabilities match the

process requirements

– Establish clear lines of

communication and

transparency

– Meet GMPs

4

Fulfillment of Drug Owner and

CMO Responsibilities • Whose SOPs do you follow?

• Have you inadvertently included loopholes in the quality

agreements and contracts?

• Do you accept work as a CMO or give work as a drug

owner and know that CGMPs cannot be followed?

• Do you know the laws and regulations required to

complete the work?

• Does your paradigm accept that low cost may lead to

low quality?

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Recalls associated with CMOs

One contract packaging site caused packaging mix-ups

accounting for approximately 670 recalls.

Single firm recalls more than 800 products resulting from Penicillin cross-contamination. Also, one firm recalls 114

products for microbial contamination of non-sterile products.

Two firms with over 850 products for Penicillin cross-contamination

and bacterial contamination in alcohol pads.

*Quarter 3

One contract manufacturer accounted for 1335 product recalls resulting in various CGMP violations discovered

during an inspection. Also, one tablet manufacturer recalled 190 Rx products.

One contract repackager caused label mix-ups

.

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Drug Owner Audit Program

Effectiveness • Do you rely upon paper audits or on site inspections?

• Are your internal auditors trained and effective?

• Are your internal auditors quality performance

measured?

• Who sees the internal audit reports?

• Who makes approval/rejection/disqualification

decisions?

• What priority do you give to fixing identified deficiencies?

• Do you measure the internal audit programs of your

CMOs?

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8

Mutually Beneficial Partner

Quality System • Quality agreements and contractual

arrangements

– Forethought and good planning!

– Informed risk assessment

– Informed decisions

– Knowledge management

– Well developed communication system within

the drug owner’s company and between the

drug owner and it’s CMO partners.

Would you want these products

from your CMO?

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Or these drug products?

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Would you want this firm as your

CMO partner?

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Or this firm?

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Acknowledgements

• Rick Friedman

• David Doleski

• Larry Ouderkirk

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