Transcript FDA biotech - San Diego Unified School District

PATHWAY TO NEW PRODUCTS
The FDA
The Biotechnology Company Life Cycle
Adapted in part from FDA Test tube to Patient
Regulation of the Product
FDA Regulates the Industry
• Traditional Expectations:
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drugs are effective and safe.
high quality.
Generic -prices reasonable.
All advertising informative
• Evolving Expectations :
– access to investigational drugs.
– High-quality information for groups
– protect human subjects
Before the FDA
• Upton Sinclair “The Jungle”
• Published only in magazines
(newspapers were worried about
advertising revenues
MILESTONE: Food Drug and Cosmetic Act (FD&C Act) of 1906
a labeling law! Not safety and efficacy
In 1927 Food and Drug Administration (FDA)-enforce food and drug
laws.
1938-Safety and studies
Milestone in 1962
Kefauver-Harris Drug Amendments to the FDCA
• testing in animals before humans
• Required clinical trial supervision and
informed consent
• Required proven EFFICACY
• Required reporting of adverse events
• Gave FDA authority to regulate advertising
The Regulatory Agencies
The USDA (US Dept. of Agriculture regulates plant pests,
plants, and veterinary biologics.
The EPA (Environmental Protection Agency) regulates microbial
and plant pesticides, new uses of existing pesticides and novel
organisms.
The FDA are responsible for food, feed additives, veterinary drugs, human drugs and medical devices.
Recombinant DNA Advisory Committee: Safety of Genetically Manipulated Material
Drug Approval and Development
Process Takes 8-20 Years
The FDA's Drug Review Process: Ensuring
Drugs Are Safe and Effective
Drug Review Steps
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Preclinical (animal) testing.
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An investigational new drug application (IND) outlines what the sponsor of a new drug
proposes for human testing in clinical trials.
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Phase 1 studies (typically involve 20 to 80 people).
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Phase 2 studies (typically involve a few dozen to about 300 people).
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Phase 3 studies (typically involve several hundred to about 3,000 people).
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The pre-NDA period, just before a new drug application (NDA) is submitted. A common
time for the FDA and drug sponsors to meet.
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Submission of an NDA is the formal step asking the FDA to consider a drug for marketing
approval.
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After an NDA is received, the FDA has 60 days to decide whether to file it so it can be
reviewed.
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If the FDA files the NDA, an FDA review team is assigned to evaluate the sponsor's
research on the drug's safety and effectiveness.
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The FDA reviews information that goes on a drug's professional labeling (information on
how to use the drug).
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The FDA inspects the facilities where the drug will be manufactured as part of the approval
process.
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FDA reviewers will approve the application or find it either "approvable" or "not
approvable."
How Much Time and Financing?
The New Drug Application (NDA)
NDA Contents
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The contents of the NDA include:
Pre-clinical
Clinical
Descriptions of proposed wording for package insert and
labeling
Index;
Summary;
Chemistry, manufacturing and control (CMC) information
Samples, Methods Validation Package, and Labeling;
Human Pharmacokinetics and Bioavailability;
Microbiology (for anti-microbial drugs only);
FDA Requires cGMP Manufacturing
Why? To insure what you sell is the same as what
you tested (Phase 3)
cGMP: Control the Process
Man
Materials
THE PROCESS
Machine
(something happens here)
Output
Methods
Environment
The process is inextricably linked to the people that use
the materials that go into it, the equipment that's
involved, the procedures and settings that are defined,
and all the attendant environmental conditions that are
present during the process.
Cells Growing-Scale UP
Spinners flasks
Cell Scale Up
Process Development
The Factory
Big Bioreactors Same Principles
Areas are Classified to Cleanliness
Purification
Purification
And Finally Product!
The Quality Unit cGMP
Insure it’s the Same as in Phase 3
• Includes QA and QC
• Maintains the records that prove that
you
– Say what you do =SOPs,
– Do What you say=Quality Products Pass Tests
– Can Prove it=Document It!
• Have Processes to Manage
Inevitable Change CAPA (Corrective
and Preventative Action)
The Quality Control Unit
Documentation
And How Do They Know its the
Same as Phase 3?
Audits
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Internal audits
Supplier/customer audits
Regulatory audits—FDA, EMEA, etc.
FDA cGMP Inspections
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Pre-Approval inspection (PAI)
Biennial inspection.
Full inspection:
Abbreviated inspection
To Meet the Federal Regulations
21CFR 210 and 211
The Biotech Company must Prove that their
Product Safety and Efficacy-Clinical Trials
Then there needed to be control on the
processes used to make sure the products
have ongoing:
– Safety
– Efficacy
• cGMP Good Manufacturing Practices
GMP Simplified!
• say what you do
• do what you say
• document it
Or.. If you didn’t write it down… you didn’t do it!
Consequences of
Noncompliance: Chain of Events
Handy List of Good
Documentation Practices
adapted from M. Fino MiraCosta Biotech
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Follow directions as written
Document everything thoroughly and completely. Use black or blue ink – follow your company’s
procedure. Pencil = not okay
Write clearly and legibly
If you deviate from a documented procedure, write it down and let the supervisor know ASAP
Do not prerecord information
Fill in all the blanks. If necessary, write “NA”, your initials, and the date
To make a correction, draw a line through it once (so you can still read the original remark) clearly
write the correction, initial, and date your entry.
Any non-self-explanatory corrections should be explained in a Comments section
Record data upon receiving them. Do not wait until the end of a shift or lunch to record
information.
Record data directly onto the approved form, batch record, or log book.
Do not write data on stick notes, scratch paper, etc.
Use the most recent version of a form. Do not stockpile personal copies of SOPs or forms – they
will change frequently
Follow your company’s dating preference:
In the US, 6/10/02 is interpreted as June 10, 2002 but in Europe, the same abbreviation is
October 6, 2002
Summary: Pathway to Products
• Producing a regulated product is risky
• You need a sound ‘concept’, a successful
‘trial’, and a good ‘process’. And and good
management to get you to the goal without
running out of $$.
• Consequences of Not Doing So are $$$$$
Adapted in part from FDA Test tube to Patient
Intellectual Property to Protect Your Product and Process is also required!