Vision For The Future

1
Vision For The Future

• Maxine M. Gallagher
• Vice President, Regulatory Affairs
• West Pharmaceutical Services, Inc.

2
Vision

• 1. The faculty of sight something that is or has
  been seen
• 2. Unusual competence in discernment or
  perception
• 3. The manner in which one sees or conceives of
  something
• 4. The mystical experience of seeing as if with
  the eyes of the supernatural or a supernatural
  being
• 5. A person or thing of extraordinary being
• 6. A mental image produced by the imagination

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Break-out Session Summary

• Top 3 discussion items from each group

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DMF 101

• How your DMF is filed and maintained at FDA
• Change control What kind of change requires
  customer notification and communication with FDA
  and the applicant
• More specific guidance on
• how to manage change
• uniformity of FDA required content
• while minimizing business disruption to the
  applicant

5
Type II

• What type of changes are covered under BACPAC?
• How will the ICH common technical document impact
  the DMF?
• When is a DMF required for an intermediate?

6
Type III

• Is compliance with cGMPs and supportive data less
  critical as you get further back in the chain?
  Is dosage form and route of administration
  dependent?
• Regarding LOAs
• Should they be generic or product specific?
• Have expiration dates?
• Should a contact be specified?
• Is the DMF the best vehicle for change control?

7
Type IV

• Regarding the IPEC Excipient Master File Guide
• Work with FDA to improve Type IV DMFs and to
  expand the application of this guide to Europe
  and Japan
• Develop a procedure for an independent review of
  excipients similar to the Cosmetic Ingredient
  Review (CIR), FEMA or GRAS expert panel review
• Encourage the development of new excipients

8
Type IV, Continued

• There is no explanation as to why refuse to
  file letters are issued for ANDAs because the
  gate keeper will not use the DMF to determine
  that the check off questions are answered
• The FDA Inactive Ingredient Guide (IIG) needs to
  be updated and made publicly available. The IPEC
  proposed changes, such as deleting the number of
  NDAs and listing the maximum level for excipients
  should be implemented.

9
Type V

• There is a definite disconnect among FDA Centers,
  specifically CBER and CDER as to how Type V DMFs
  are required/utilized
• Industry needs direction per FDA Centers as to
  when Type V DMFs are appropriate for submission
• There is a need to define the appropriate
  contents for inclusion in Type V DMFs. Should
  these include
• Repetitive processes
• Proprietary information
• Site information

10

• The correlation of information in a DMF with that
  in the corresponding CMC section of a marketing
  application requires communication and
  cooperation between the Holder and the Applicant.
  The following are suggestions to facilitate a
  seamless interface between the DMF and the
  applicable CMC section of the marketing
  application.

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Know Your Source. And not just on paper!

• Particularly important for foreign sources and
  new companies
• Understand the product and/or service being
  purchased
• Perform an audit assure compliance to CGMPs,
  drug, biologic or other applicable standards

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Communication

• Calling and asking for a LOA isnt enough!
• Talk to the right person(s)! Purchasing to
  purchasing may not be the best approach!
• Establish contacts in appropriate functional
  areas such as RA and Technical Support
• Define your requirements and expectations Be
  specific and dont make assumptions!

13
Communication

• Be candid and realistic about product(s) and
  capabilities.
• Determine if there is a DMF, if it is current,
  and accurately describes the product and/or
  process.
• Determine when the last update annual or
  technical amendment was filed.
• Determine when, if applicable, the last FDA
  deficiency letter was received and a response
  filed.

14
Communication

• Ask questions and discuss matters relating to
• Quality
• Documentation
• Administration
• Education/Training
• Expectations

15
Quality

• Quality is the mutual responsibility of the
  Holder and Applicant.
• The Holder has the responsibility for the product
  or process they are providing.
• The Applicant has responsibility for the final
  dosage form.

16
Quality

• Tools and information utilized to assure that
  appropriate quality systems and controls are in
  place include
• -Audit(s)
• -Questionnaires
• -Statements of compliance to applicable
• standards such as CGMPs,
• -ISO certification

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Quality

• The Holder and Applicant must assure that
  appropriate controls are in place to maintain
  consistency in the product or service being
  provided. Otherwise, the final dosage forms
  physical, chemical or performance characteristics
  may be affected.

18
Documentation

• Remember the first rule of CGMPs If it isnt
  documented, it hasnt been done!
• Information in DMFs should be specific to
• the product or process.
• Ask whats filed in the DMF!
• Determine if the DMF information is
• compatible with the marketing application.

19
Documentation

• Determine whats not filed in the DMF!
• Determine if theres a process in place to
  provide information required for the marketing
  application that is not filed in the DMF.
• Determine who will be responsible for providing
  that information.

20
Administration

• The DMF format should be user friendly.
• The DMF should contain all of the required
  elements such as a statement of commitment,
  contact information, etc.

21
Administration

• The DMF contents should satisfy the requirements
  of applicable FDA and ICH guidances (e.g.
  Container/Closure Guidance, 1999)
• The Holder should understand the relevance of
  guidances such as the Post Approval Change
  Guidance (1999) and BACPAC, for example, to the
  specific type of DMF.

22
Administration

• The DMF should be structured to contain
  information that will cross FDA Centers.
• The Holder should have a written procedure for
  change control.
• The Holder should have a written policy for
  customer notification.

23
Administration

• The Holder should employ individual(s) with
  sufficient experience and training
• - That are familiar with FDA processes and
  policies
• - To administer the DMF, i.e., write and
  submit LOAs, annual, and technical amendments
• .

24
Administration

• - To provide ongoing support to
• Applicants
• - To inform the business of regulatory
• changes and assure compliance in a
• timely manner
• - That know their way around FDA

25
Education

• Educate employees and vendors about your product
  and the role of applicable guidances in
  regulating them.
• Educate employees and vendors about the
  respective roles of CGMPs and guidances in
  producing and controlling your products and
  processes.
• If you dont know how to do it, seek professional
  advice.

26
Education

• Stay informed of current regulations and
  guidances applicable to your product and/or
  processes by
• - Reading trade magazines and periodicals
• - Participating in seminars and meetings
• - Visiting the FDA web sites
• - Joining organizations such as DCAT,
• PhRMA, IPEC, etc.

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Expectations

• All products are not created equal! A polymer is
  not a drug product!
• Understand the product and process
• and assure that applicable controls and
• standards that assure quality and
• consistency are in place.
• Do not impose requirements on the DMF
• Holder that cannot be achieved.

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Expectations

• One size does not fit all!
• Your way is not the only way to produce and
  document a product or process.
• The cost of the product or service is directly
  proportional to the quality and support you
  require. Expect to pay more as regulatory and
  industry requirements accelerate.

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DMF Wish List

• A rewrite of the 1989 DMF Guidance that
• - incorporates the DMF requirements outlined
• in newer guidances (e.g. 1999
• Container/Closure Guidance)
• - Defines DMF requirements specific to the
• Type of DMF example Draft Type V DMF
• guidance issued by CBER
• - Includes Industry input

30
DMF Wish List

• A FDA sponsored educational seminar for FDA
  reviewers, DMF users and DMF holders that
  defines FDA expectations and practices
• A global DMF system established through the ICH
  that would facilitate the filing and approval of
  international marketing applications

31
DMF Wish List

• That the Type III Packaging committee formed as
  a part of this industry workshop will not
  disband, but will continue as a forum for
  applicants and holders to exchange ideas and
  improve regulatory processes for packaging.

32
Basic Requirements

• Know your source.
• Talk to the right person(s).
• Determine if the Holder is familiar with
  applicable guidances and regulations for specific
  DMF types.
• Define your requirements and expectations up
  front!

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Basic Requirements

• Ask the right questions about the DMF quality,
  documentation and administration.
• Determine whats in the DMF.
• Identify who will provide the required
  information and in what form.

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Basic Requirements

• Assess the qualifications and training of
  personnel.
• Perform a quality audit.
• Assure that the Holder has appropriate quality
  systems in place to assure product or process
  consistency.

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DMF Basics

• Quality is everyones responsibility but the
  ultimate responsibility resides with the
  Applicant. However, we all need to do our
  homework for ...
• DMF to CMC