Preparing For The RAC Exam: Regulatory Impact On Business

Preparing for the RAC Exam
Regulatory Impact on Business:

Points to Consider
when preparing for the RAC Exam
presented by
Robert J. Michalik, Esq., RAC
RegulatoryPro.com
RAC Exam Preparatory Course:
Regulatory Impact on Business &
Points to Consider when Preparing for the Exam
Biographical Summary
March 21, 2009 2

Goal of this presentation:

During this presentation we will use the content outline as a
framework to discuss specific points that relate to:
• the business aspects of regulatory affairs
• Highlight specific issues and topics that should be carefully

considered when applying regulatory knowledge to the
design, development, testing and submission of registrations
to FDA in support of a FDA-regulated product, and
• Point out specific sections of the law (statutes and

regulations) that deserve closer review to better prepare for
the RAC (US) exam.
March 21, 2009 3

RAC (US) Examination Content Outline:

RAPS Certification Committee provides this content outline as a
primer for applicants to focus their review of legal, regulatory and
practical areas likely to be covered on the exam
1. STRATEGIC PLANNING
2. DESIGN and DEVELOPMENT
3. PREMARKET / REGULATORY REVIEW
4. MANUFACTURING / QUALITY SYSTEMS
5. MARKETING / POST-APPROVAL
6. INTERFACING [with Regulators and Colleagues]
The content outlines can serve as a helpful tool for assessing your
knowledge base and identifying your areas of strength and weakness
in preparing a study plan.
March 21, 2009 4
“Business goals and Regulatory Strategies are integrally related to each other”
• The universal Business goal:

Maximize shareholder value with minimal costs
and risks to the company.
• Regulatory Affair’s primary objective is

simple:
Obtain and maintain marketing authorization in a
cost/effective way and with the lowest risk to the
company.
Prerequisites to achieving your regulatory objective are two-fold:
1. Properly classify your product
2. Select the most appropriate regulatory pathway
March 21, 2009 5
The RAC (US) exam focuses heavily on issues

relating to regulatory strategic planning. Key
topics and issues that RAC exam candidates
will be challenged include the following:
a. Identification of the various Product Classifications for
drugs, biologics and medical devices; and
b. Assess your understanding of the array of Regulatory

Pathways and Regulatory Options available to bring a
product to market.
March 21, 2009 6

Figuratively speaking, Regulatory Affairs professional select the regulatory

options (levers) to use to control new product development and registration
March 21, 2009 processes. Which levers to employ depend upon a variety of factors. 7
a. Product Classification
Preparing a successful regulatory strategy that leads to FDA

marketing authorization depends upon several factors,
including what TYPE of product is to be developed.
– Ask yourself, “Is my product a …”
• Drug (which subcategory of drug is it?)
• Biologic (proprietary, “follow-on” biologic, true biologic
vs. drug manufactured using biological systems
• medical device (Class I, II or III),
• combination product (test: “primary mode of action”),
• human cellular or tissue-based products (HCTP)
• Other (cosmetic,food, nutriceutical, nutritional
supplement, etc)
Strongly recommend examiners carefully review product definitions in the following statutes:
Food, Drug & Cosmetic Act: http://www.fda.gov/opacom/laws/fdcact/fdcact1.htm (section II)
Public Health Service Act, 42 USC sec. 262(i) http://www.fda.gov/opacom/laws/phsvcact/phsvcact.htm (
March 21, 2009 8
a. Product Classification
Ultimately the correct product classification will depend

heavily upon the marketing and performance claims you
expect to make when promoting your product to the user, the
consumer, and to the public at large.
Properly identifying the class and subclass of product to be

developed will ensure that you and the development team will
be applying the appropriate regulatory requirements as you
proceed in the development effort.
Always first compare the product structure and expected

marketing claims for the new product with the legal definitions
for the type of product.
March 21, 2009 9

b. Regulatory Pathways / Regulatory Options
Which way should you go?
March 21, 2009 10

You have properly classified your product by analyzing its characteristics and purported benefits based upon marketing claims.
Now you should consider the following issues to craft an effective regulatory strategy to bring your product through the
development process.
b. Regulatory Pathways / Regulatory Options
i. Advise management on requirements and options for regulatory submissions / approvals

(e.g., local, national, international).
ii. Analyze laws, regulations and guidelines for compliance requirements.
iii. Develop effective regulatory submission strategies for timely FDA product review.
iv. Perform benefit / risk analysis of options for regulatory compliance.
v. Prepare justification for accelerated mechanisms for review.
vi. Develop and implement global regulatory strategy.
vii. Interface with marketing and manufacturing to assure development plans are in
alignment with objective/capabilities
March 21, 2009 11
Comparison of Product Class and Registration Option
Risk Marketing Biologic*

Drug Medical Device
Level History
Class III medical device;
Unknown New drug New biologic (drug)
FD&C Act §513(a)(1)(C)
(no safety or FD&C Act §505(b)(1) PHS Act §351
Highest §515
efficacy 21 CFR Parts 50, 56, 58, 210, 21 CFR Parts 50, 56, 58, 210,
21 CFR Parts 812, 814
data) 211, 312, and 314 211, 312, and 314
plus Class II requirements
Modified biologic or
Generic biologics (“follow
on” biologic)
Modified drug
Somewhat Class II medical device; Could use NDA per FD&C
FD&C Act §505(b)(2)
known FD&C Act §513(a)(1)(B) Act 505(b)(1) or BLA
21 CFR Parts 50, 56, 58, 210,
(related safety §510(k) per PHS Act
Moderate 211, 312, 320 & 330
and §514 §351; Few exceptions under
Generic drug
efficacy 21 CFR Parts 800, 801, 803, FD&C Act §505(b)(2)
FD&C Act §505(j);
data exists) 806, 807, 820 and 860 No legal basis for reduced
21 CFR Parts 320 & 330
regulatory requirements
for modified biologics at
this time.
Well known “Over the Counter” (OTC) Class I medical device; Nutriceuticals / herbal
Generally drug FD&C Act §513(a)(1)(A) supplements ?
Regarded FD&C Act §§501, 502, 510, 516, 518, Currently regulated as food;
Lowest
as Safe & §201(p)(1) 519, and 520 possible statutory
Effective Compliance with Drug 21 CFR Parts 800, 801, 803, changes under
March 21, 2009 (GRASE monographs 806, 807, 820 and 860 consideration12
a. Documentation (GxP compliance)
i. Advise master file sponsor of regulatory requirements.
ii. Ensure specifications / methods for testing of active pharmaceutical ingredients (API)
comply with regulatory requirements.
iii. Evaluate manufacturing changes for regulatory filing strategies.
iv. Ensure procedures for appropriate change control systems are in compliance.
v. Ensure clinical trial design, conduct and documentation are in compliance with GCPs.
vi. Obtain required clinical research and associated documentation (e.g., IRB and
financial disclosure documentation).
vii. Write/review SOPs for compliance with GCPs and regulatory affairs practice.
viii. Ensure appropriate record retention.
March 21, 2009 13


b. Testing Requirements / Compliance
i. Determine testing requirements with regard to:

1. clinical safety and efficacy (e.g., GCPs); and
2. nonclinical safety (e.g., GLPs).
ii. Ensure compliance and adequacy of documentation regarding:

1. clinical safety and effectiveness (e.g., GCPs, IRBs);
2. Internal / external laboratories;
3. nonclinical safety and effectiveness (e.g., preclinical studies, analytical
methods and GLPs); and
4. product (e.g., drug GMPs / QSR and device specifications).
iii. Ensure nonclinical data supports initiation of the proposed clinical program.
iv. Recommend relevant biocompatibility assessments for medical devices.
v. Monitor clinical trial batch in compliance with GMPs/QSRs.

March 21, 2009 14

b. Testing Requirements / Compliance
This familiar graphic posted on FDA’s website provides a comprehensive outline of the
development process for a new drug. Your design plan is integrally tied to the product
classification you’ve identified.
March 21, 2009 15

a. Regulatory Authorities, Vendors and Subcontractors
i. Monitor applications under regulatory review.
ii. Negotiate/interact as appropriate with regulatory authorities during the

review process.
iii. Negotiate labeling claims between government agencies and company.

iv. Ensure raw materials, services, and subcontracted activities comply with
applicable regulations and specifications.
March 21, 2009 16


b. Submission / Listing / Registration / Obtaining Marketing Clearance or Approval
i. Determine acceptability of biologic, medical device or pharmaceutical premarket data.
ii. Prepare premarket submissions and master files for drugs, biologics and medical devices.
iii. Review applications for completeness according to “refuse-to-file” guidelines.
iv. Ensure readiness for preapproval inspections.
v. Oversee and advise on processes to allow electronic submissions.
vi. Ensure procedures in place for appropriate responses to Regulatory Agency Queries.
vii. Prepare and submit forms for drug and device listing and establishment registration.
viii. Ensure clinical trial monitoring and clinical trial audits are performed.
March 21, 2009 17


Premarket Product Development Activities are constantly being
reassessed from a business and ethical perspective …
Regulatory Affairs
The RAC Exam will include questions that test your knowledge
of practical aspects of compliance and strategy. To respond,
March 21, 2009 18
consider
a. Documentation Regulatory
Mgmt
b. Training
c. Compliance ‘the box” of laws
and regulations
(FD&C Act & 21 CFR)
Corp. Mgmt
March 21, 2009 19


a. Documentation (GxP compliance)
i. Establish and ensure development of SOPs necessary for regulatory
compliance (e.g., alerts, GMP/QSR compliance, recalls, etc.).
ii. Ensure/develop internal audit procedures to ensure regulatory compliance

(e.g., GMPs/QSRs).
iii. Develop procedures for audit of vendors, suppliers or contractors.
iv. Develop records retention policies and procedures that minimize risks (e.g.,
product liability discovery) and ensure regulatory compliance.
b. Training
c. Compliance
March 21, 2009 20

a. Advertising / Promoting / Labeling

b. Post-marketing Surveillance/Vigilance
c. Distribution
d. Post-marketing / Maintenance:
e. Crisis Management
March 21, 2009 21

a. Advertising / Promoting / Labeling
i. Approve advertising/labeling/promotional items for compliance before release.
ii. Develop Freedom of Information Act strategy regarding:

1. confidentiality and protection of proprietary information, and
2. document requests.
iii. Evaluate data to support comparative claims in advertising.
b. Post-marketing Surveillance / Vigilance

i. Ensure that appropriate systems are in place to document and track product
complaints and ADR reports.
ii. Ensure implementation of necessary corrective actions based on results of

inspections, audits and failure analysis.
iii. Report product safety issues/failures to regulatory agencies as required.

March iv.
21, Review
2009 adverse drug reaction reports and medical device reports. 22
c. Distribution
i. Comply with import/export requirements.

i. For example, What “tier” has the export country been assigned by
FDA based upon the government’s ability to manage regulated
products?
iii. Review regulatory aspects of contracts for product distribution

(e.g., product complaints, product tracking, etc.).
Will your company manage the complaint and reporting process
or will you assign those responsibilities to a third-party partner?
iv. Advise on the issues related to drug / product / lot releases.

Do special conditions apply to your product related to lot release?
v. Ensure adequacy of product traceability systems.
March 21, 2009 23

Regulatory affairs should closely monitor supply chain processes to ensure
compliance. Potential conflicts and practical problems that arise during
post-approval phases provide a good source of questions by RAC
examiners.
March 21, 2009 24

d. Post-marketing / Maintenance:
i. Submit required periodic reports and updates (e.g., PSURS, master files,
etc.).
ii. Comply with product post-marketing approval requirements.
iii. Ensure regulatory compliance of post-approval marketing studies.
iv. Prepare strategy and policy for alerts/notifications/recalls/market
withdrawals.
v. Implement and monitor effectiveness of alerts/notifications/recalls.
vi. Advise management on alerts/notifications/recalls.
e. Crisis Management
i. Advise management regarding the regulatory impact of a crisis event.
ii. Advise management on regulatory implications of proposed crisis resolution
strategies.
iii. Participate in the development and functioning of the crisis management
program.
March 21, 2009 25

6. INTERFACING
[with Regulators and External Organizations]
a. Regulatory Agencies
b. Regulatory Authority Inspections
c. Government and Public Relations
d. Inter-departmental Guidance
e. Standards Organizations
March 21, 2009 26

End of Part I: Regulatory Impact of Regulations on Business
Start of Part II: Points to Consider / Study Recommendations
March 21, 2009 27

Title 21 Code of Federal Regulations

Recommended Sections to Review to prepare for the Exam
All sections of the regulations are fair game for examination as part of the
RAC Certification process. However, in my opinion, certain Parts and
sections are more relevant to the practice of Regulatory Affairs on a day-
to-day basis and therefore should be more carefully studied during your
exam preparation.
March 21, 2009 28

Title 21 Code of Federal Regulations

Recommended Sections to Review to prepare for the Exam
Review Guide
Should review
Recommended
review
Must review
March 21, 2009 29

Recommended CFR Sections to Review

General, Administrative and enforcement (21 CFR Parts 1-99)
Review Guide
Should review
Recommended
review
Must review
March 21, 2009 30


GCP, GLP, Patent Term restoration, Color additives, etc
(21 CFR Parts 1-99)
Review Guide
Should review
Recommended
review
Must review
March 21, 2009 31


Drug Labeling, Advertising, Marketing, Registration and GMPs
(21 CFR Parts 200 - 299)
Review Guide
Should review
Recommended
review
Must review
March 21, 2009 32


New Drug Products (21 CFR Parts 300 - 369)
Review Guide
Should review
Recommended
review
Must review
March 21, 2009 33


Biological Products; Blood Products, Cosmetics
(21 CFR Parts 600-740)
Review Guide
Should review
Recommended
review
Must review
March 21, 2009 34

Recommended Regulatory Review –

Medical Devices (21 CFR Parts 800 – 1272)
Review Guide
Should review
Recommended
review
Must review
March 21, 2009 35

Recommended Regulatory Review –
Radiological Health Products

(21 CFR Parts 1000 – 1050)
Review Guide
Should review
Recommended
review
Must review
March 21, 2009 36

Human Cell, Tissues & Cellular and Tissue-based Products

(21 CFR Parts 1270-1271)
Review Guide
Should review
Recommended
review
Must review
March 21, 2009 37

Actual Question from most recent exam (Sept 2008)
“Responsible Corporate Officer” doctrine is applied by courts in which the

knowledge of non-compliance or other wrong doing may be inferred merely from
the position of responsibility and authority that the responsible corporate officer
holds within a company. See United States v. Park, 421 U.S. 658 (1975)
A question referring to the RCO doctrine may be asked in relation to whether a

CEO has legal responsibility and can be criminally liable for an act or acts that he
is not actually aware of by virtue of high position in the company or geographic
distance to the wrong doing.
March 21, 2009 38

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Preparing for the RAC Exam

Regulatory Impact on Business:

March 21, 2009 2

Goal of this presentation:

• the business aspects of regulatory affairs

• Highlight specific issues and topics that should be carefully

• Point out specific sections of the law (statutes and

March 21, 2009 3

RAC (US) Examination Content Outline:

• The universal Business goal:

• Regulatory Affair’s primary objective is

The RAC (US) exam focuses heavily on issues

b. Assess your understanding of the array of Regulatory

March 21, 2009 6

Figuratively speaking, Regulatory Affairs professional select the regulatory

Preparing a successful regulatory strategy that leads to FDA

Ultimately the correct product classification will depend

Properly identifying the class and subclass of product to be

Always first compare the product structure and expected

March 21, 2009 9

March 21, 2009 10

b. Regulatory Pathways / Regulatory Options

i. Advise management on requirements and options for regulatory submissions / approvals

ii. Analyze laws, regulations and guidelines for compliance requirements.

iv. Perform benefit / risk analysis of options for regulatory compliance.

v. Prepare justification for accelerated mechanisms for review.

vi. Develop and implement global regulatory strategy.

Comparison of Product Class and Registration Option

Risk Marketing Biologic*

2. DESIGN and DEVELOPMENT

a. Documentation (GxP compliance)

i. Advise master file sponsor of regulatory requirements.

iii. Evaluate manufacturing changes for regulatory filing strategies.

viii. Ensure appropriate record retention.

March 21, 2009 13

2. DESIGN and DEVELOPMENT

i. Determine testing requirements with regard to:

ii. Ensure compliance and adequacy of documentation regarding:

iv. Recommend relevant biocompatibility assessments for medical devices.

v. Monitor clinical trial batch in compliance with GMPs/QSRs.

2. DESIGN and DEVELOPMENT

March 21, 2009 15

3. PREMARKET / REGULATORY REVIEW

a. Regulatory Authorities, Vendors and Subcontractors

i. Monitor applications under regulatory review.

ii. Negotiate/interact as appropriate with regulatory authorities during the

iii. Negotiate labeling claims between government agencies and company.

March 21, 2009 16

3. PREMARKET / REGULATORY REVIEW

i. Determine acceptability of biologic, medical device or pharmaceutical premarket data.

iii. Review applications for completeness according to “refuse-to-file” guidelines.

iv. Ensure readiness for preapproval inspections.

v. Oversee and advise on processes to allow electronic submissions.

March 21, 2009 17

3. PREMARKET / REGULATORY REVIEW

4. MANUFACTURING / QUALITY SYSTEMS

March 21, 2009 19

4. MANUFACTURING / QUALITY SYSTEMS

ii. Ensure/develop internal audit procedures to ensure regulatory compliance

iii. Develop procedures for audit of vendors, suppliers or contractors.

March 21, 2009 20

a. Advertising / Promoting / Labeling