Pharmaceutical Nomenclature Issues and challenges

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Pharmaceutical NomenclatureIssues and challenges

• Moheb M. Nasr, Ph.D.
• Acting Director
• Office of New Drug Chemistry (ONDC)
• OPS, CDER, FDA
• Advisory Committee for
• Pharmaceutical Sciences (ACPS)
• October 22, 2003

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Pharmaceutical Nomenclature Issues and
challenges

• FDA Perspective
• Orally Disintegrating
• Tablets (ODT)
• Topical Dosage Form
• Classification - an Update
• Committee Discussions

Dan Boring, R.Ph.,Ph.D. Frank Holcombe, Jr.,
Ph.D. Lucinda Buhse, Ph.D.
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Issues and challenges

• Impact on regulatory decisions, marketing, drug
  development, and the public
• Nomenclature development (scientific and
  regulatory challenges)
• How to do it right the first time?
• Is a new dosage form needed or is it just a minor
  modification in an existing dosage form that can
  be handled by labeling?
• How to establish definitions and criteria for new
  dosage forms?
• Do we need to have that many dosage forms?

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Issues and challenges

• Coordination with different organizations and
  stakeholders
• Definitions (descriptive and quantifiable
  attributes)
• Refinement and/or replacement of older dosage
  forms
• Pharmaceutical equivalence issues

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Questions for ACPS

• 1. What are the factors that the Agency should
  consider in determining (a) whether a new dosage
  form name is warranted and (b) how such a dosage
  form should be defined?
• 2. Is it reasonable or useful to include a
  quantifiable attribute when defining a dosage
  form or distinguishing between closely related
  dosage forms where appropriate? Can such an
  approach be viewed as too arbitrary in some cases
  and too rigid in other cases?

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Questions for ACPS

• 3. Is the proposed criterion, i.e., an in vitro
  disintegration time of less than 60 seconds,
  reasonable for defining an orally disintegrating
  tablet?
• 4. Has the update on topical dosage forms
  presented today addressed the questions/comments
  raised by the ACPS at the March 2003 meeting?

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FDA Perspective on Dosage Form Nomenclature

• Dr. Dan Boring, R.Ph., Ph.D.
• Review Chemist Labeling Expert
• ONDC, OPS

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Nomenclature ofPharmaceutical Dosage Forms

• Issues and challenges
• Scientific
• Regulatory
• Marketing
• Legal
• Healthcare provider
• Patient

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What is an Established Name?

• The FDC Act states drug only
• Drug substance and/or drug product?
• At CDER, an established name for both drug
  substance and drug product
• In general, an established name for a drug
  product is
• (drug substance) (release characteristic)
• (route of administration) (dosage form)
• Todays focus is on dosage form

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Definition ofa Pharmaceutical Drug Product

• Drug Product is defined as a finished dosage form
  such as tablet, capsule or solution
• What is a dosage form?
• A dosage form could be defined as the physical
  form of a drug product at the point that it is
  introduced into the body, or, where final
  preparation is required before introduction into
  the body, the physical form of the drug product
  in the package that bears instructions for final
  preparation (private communication)
• Dosage forms are non-proprietary

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Stakeholders

• Innovators
• Research, development, marketing, legal
• FDA
• OND, ONDC, ODS, COS, NSC
• USP
• Expert Comm on Nomenclature and Labeling
• Healthcare providers and patients
• Not direct participants

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FDA Nomenclature Issues

• New drugs
• No USP monograph exists
• Is a new name necessary?
• Is it nomenclature or labeling?
• Generic drugs
• Compliance with USP monograph?
• Is a compendial name being developed?
• Will name allow proper product selection for
  substitution?
• Name definition should not allow generic
  manufacturers to substitute a new dosage form for
  a RLD
• OTC drugs
• Product selection by patient

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Nomenclature Assessment Factors

• Name must clearly identify the product
• Name promotes accurate recognition without risk
  of medication errors
• Name meets database, indexing and listing needs
• Name consistent with precedents (i.e., systems)
• Name should not provide an advantage through
  exclusive proprietary technology

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Challenges

• Will a new name serve long-term needs?
• Is an older term still accurate?
• Is a developing new term appropriate?
• Can objective standards be developed to define a
  new dosage form?
• How should name development be coordinated
  (innovator, FDA, USP)?
• Global harmonization?
• Implementation?

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New Dosage Forms and Drug Delivery Systems

• Orally disintegrating tablets
• Tablets for suspension
• Liposomes
• Microspheres
• Films?
• Iontophoretic systems?

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DefiningOrally Disintegrating Tablets

• Frank Holcombe, Jr. Ph.D.
• Associate Director for Chemistry
• Office of Generic Drugs, OPS

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Current Definitions of ODT

• FDA definition
• A solid dosage form containing medicinal
  substances which disintegrates rapidly, usually
  within a matter of seconds, when placed upon the
  tongue
• USP Stimuli proposal
• A solid oral dosage form that disintegrates
  rapidly in the mouth

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Desired Characteristics and Benefits of ODT

• Oral disintegration
• Rapid disintegration
• No chewing or liquids necessary
• Provides improved route of administration and
  increased compliance for certain patient
  populations

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Issues Concerning ODT

• Limited experience similarity of all initial
  products
• Expansion in product variations due to changes in
  
• Technologies
• Formulations
• Additional drug products
• Target market population

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Issues Concerning ODT

• Format of suitable definition
• Should address both the desired characteristics
  and control of extent of product range
• Must address
• Method of administration
• Objective criteria (limits for disintegration
  time)

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Issues Concerning ODT

• Disintegration evaluation
• In-vivo testing (subjective, objective)
• In-vitro testing (objective)
• Variety of methods
• Results may be method dependent

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In-vitro Testing Methods

• Applicant in-house methods (proprietary)
• FDA laboratory method (static)
• USP Chapter lt701gt Disintegration (dynamic)

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In-vitro Testing Results

• Static 1-78 sec
• Dynamic 1-69 sec
• Most products in 1 to 30 sec range
• No data correlating in-vivo and in-vitro
  disintegration times

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In-vitro Testing Results
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FDA Proposal

• A revision of the ODT definition to include
  in-vitro disintegration method and acceptance
  criteria (USP lt701gt, lt 60 sec) Objective
• To provide criteria (based on original
  expectations) for distinguishing orally
  disintegrating tablets from other tablet forms

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Topical Dosage Form Classification an Update

• Lucinda Buhse, Ph.D.
• Acting Director
• Division of Pharmaceutical Analysis
• Office of Testing and Research, OPS

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Advisory Committee Input

• No need to include appearance and feel (e.g.,
  greasy, non-greasy)
• Definitions should be based on the vehicle
• Ointments and suspensions could be classified as
  lotions (an overused term)
• Do not make cream a default definition and do not
  separate creams using hydrophilic-vs-hydrophobic
• Use detailed rheological evaluation (e.g., yield
  values) to distinguish gels and/or lotions from
  creams
• Reconsider criteria used to classify gels

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CDER Activities

• Evaluation of ACPS input
• Consultations with Dr. Arthur Kibbe
• Analysis of liquid/semi-solid borderline products
  based on more extensive rheological evaluation
• Examination of optical properties and
  compositions of gels

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Rheological Evaluation
Sample Yield Value (D/cm2) 1 50 29
90 62 125 61 160 36 195 50 200 51 525
4 600 32 660
Conforms to container
Does not conform to container
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Questions for ACPS

• 1. What are the factors that the Agency should
  consider in determining (a) whether a new dosage
  form name is warranted and (b) how such a dosage
  form should be defined?
• 2. Is it reasonable or useful to include a
  quantifiable attribute when defining a dosage
  form or distinguishing between closely related
  dosage forms where appropriate? Can such an
  approach be viewed as too arbitrary in some cases
  and too rigid in other cases?

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Questions for ACPS

• 3. Is the proposed criterion, i.e., an in vitro
  disintegration time of less than 60 seconds,
  reasonable for defining an orally disintegrating
  tablet?
• 4. Has the update on topical dosage forms
  presented today addressed the questions/comments
  raised by the ACPS at the March 2003 meeting?