Batch Release Testing Requirements PharMEDium Lunch and...

Batch Release Testing RequirementsPharMEDium Lunch and Learn Series

ProCE, Inc.www.ProCE.com 1

Batch Release Testing Requirements

July 14, 2017

Featured Speaker: Susan J. SchnieppDistinguished FellowRegulatory Compliance Associates, Inc.

LUNCH AND LEARN

CE Activity Information & Accreditation

ProCE, Inc. (Pharmacist and Tech CE)

1.0 contact hour

2

Funding: This activity is self‐funded through PharMEDium.

It is the policy of ProCE, Inc. to ensure balance, independence, objectivity and scientific rigor in all of its continuing education activities. Faculty must disclose to participants the existence of any significant financial interest or any other relationship with the manufacturer of any commercial product(s) discussed in an educational presentation. Ms. Schniepp has served as a consultant for Regulatory Compliance Associates, as an auditor for NSF, and as a consultant for PharMEDium Services, LLC.



3

Submission of an online self‐assessment and evaluation is the only way to obtain CE credit for this webinar

Go to www.ProCE.com/PharMEDiumRx

Print your CE Statement online

Live CE Deadline: August 11, 2017

CPE Monitor– CE information automatically uploaded to NABP/CPE Monitor upon

completion of the self‐assessment and evaluation (user must complete the “claim credit” step)

Online Evaluation, Self-Assessmentand CE Credit

Attendance Code

Code will be provided at the end of today’s activityAttendance Code not needed for On‐Demand

Ask a Question

Submit your questions to your site manager.

Questions will be answered at the end of the presentation.

4

Your question. . . ?



Resources

Visit www.ProCE.com/PharMEDiumRx to access:

– Handouts

– Activity information

– Upcoming live webinar dates

– Links to receive CE credit

5

July 14, 2017Batch Release Testing Requirements

Featured Speaker: Susan J. Schniepp

Distinguished Fellow, Regulatory Compliance Associates Inc.Parenteral Drug Association Board of Directors Member

Lunch and Learn

6



Agenda

• Background and History• Regulations and Standards• Batch Record Release Testing

o Analytical Chemistry Testingo Microbiological Testing

• Activities Supporting Batch Release• Data • Customer Impact• Summary

7

8



Background and History

• New England Compounding Centero Responsible for 2012 Meningitis Outbreako Sickened 800+ Individualso Resulted in 64 Deathso Congress passed Drug Quality & Security Act

2013• Gave FDA more authority to regulate and

monitor compounding facilitieso Owner charged with racketeering and 2nd

degree murdero Guilty of racketeering March 2017

9

10



Regulations and Standards

Food, Drug, and Cosmetic (FD & C) Act

Under section 501(a)(2)(B) of the FD&C Act, a drug is deemed to be adulterated if:

“the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice to assure that such drug meets the requirements of this chapter as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess . . . . “

11


(continued)

• Current Guidanceso 21 CFR Parts 210 and 211o Current Good Manufacturing Practice – Interim Guidance for

Human Drug Compounding Outsourcing Facilities Under Section 503B of the FD&C Act – July 2014

o Facility Definition Under Section 503B of the FD&C Act – April 2016

o Insanitary Conditions at Compounding Facilities – August 2016o Sterile Drug Products Produced by Aseptic Processing —

Current Good Manufacturing Practice September 2004.

• Example Standard o USP General Test Chapter <71> Sterility Tests

12




(continued)

• Appropriate specifications must be established for each drug product (see §211.160(b)). Specifications must address those attributes necessary to ensure the quality of the finished drug product (see §211.160(b)) and should include at a minimum:o Identity of the active ingrediento Strength of the active ingrediento Sterile drug products:

• Limit for visible particulates• Statement of Sterility• Limit for bacterial endotoxins

13

Batch Record Release Testing: Analytical Chemistry Testing

• Potency: Measure of the amount of the active ingredient(s) in a particular dosage formo Typical specification Range: 90-110% (USP)

• Identification: Definitive confirmation of the presence of the active ingredient(s) in the dosage formo Typical Specification: Conforms to Standard

(USP)14



15

16



17

Batch Record Release Testing:

Microbiological Testing

• Sterility: The absence of microbial contamination (pathogens) in the dosage formo Typical Specification: Absence of

Salmonella, E. Coli, etc.

• Endotoxin: Identification of the level of fever causing microbial by products present in the dosage formo Typical Specification: < 0.25 EU/mL

18



19

20



21

Activities Supporting Batch Release

• Equipment Installation Qualification, Operational Qualification, Performance Qualification (IQ/OQ/PQ)

• Why this is important:o Establishes the suitability of the equipmento Assures results generated are accurate

and robusto Assures manufacturing processes produce

product meeting predetermined specifications

22



23

Activities Supporting Batch Release

(continued)

• Method Validation/Verification• Why this is important:

o Assures analytical procedure suitable for iuse. o Results reflect quality, reliability and consistency

of resultso Part of good analytical practice. o Method “verification” or method “transfers” used

to transfer methods from one lab to another. o More limited and not as robust as “validation". o Verification is needed to verify laboratory

capablity

24



25

26



Activities Supporting Batch Release (continued)

• Media Fills• Why this is important:• Process control demonstrating operations in

qualified areas:• Are preformed appropriately• Cleanliness is maintained• Contamination risks not introduced by

personnel• Contamination risks not introduced by

process.27

28




• Smoke Studies• Why this is important:

o Demonstrate sufficient design and control reducing potential contamination

o Identifies potential risk areas

29

30



31


• HEPA filter data (changes and challenges) for buffer zone and laminar airflow hoods

• Why this is important:o Demonstrates operations in critical zones

and support zones are appropriately controlled to minimize potential particulate ingress.

32



33


• Particulate Monitoring • Why this is important:

o Demonstrates air quality is controlledo Particulates are not added to product

34



35


• Environmental Monitoring• Why this is important:

o provides assurance that ongoing operations are in control.

o process control o Environmental control

36



37


• Procedural Changes to SOPs:• Why this is important:

o Demonstrates continuous process improvement based on results

o Formal documentation of changes

38



39


• Pharmacist/Pharmacy Technician Training• Why this is important:

o Standard requirement o Assures personnel understand and are

capable of maintaining conditions during production that will not compromise the products.

40




• Balancing reports for air handler adjustments (or schedule when it is to be done) as well as any engineering changes done to make this meet criteria.

• Why this is important: Demonstrates appropriate pressurization can be maintained during operations.

41

42




• Cleaning/Disinfectant/Sanitization Processes• Why this is important:

o Maintains environmento Prevent cross-contamination of productso Achieves appropriate microbiological

cleanliness levels for the class of cleanroom for an appropriate period of time.

43

44



45

ALCOAData Integrity Element Description 21 CFR Reference

Attributable All data generated or collected must be attributable to the person generating the data

§§ 211.101(d), 211.122, 211.186, 211.188(b)(11), and 212.50(c)(10)

Legible All data recorded must be legible (readable) and permanent

§§ 211.180(e) and 212.110(b)

Contemporaneous results, measurements and data is recorded at the time the work is performed

§§ 211.100(b) and 211.160(a)

Original Original data, sometimes referred to as source data or primary data, is the medium in which the data point is recorded for the first time.

§§ 211.180 and 211.194(a)

Accurate complete, consistent, truthful, and representative of facts §§ 211.22(a), 211.68, 211.188, and 212.60(g)

2017 © Regulatory Compliance Associates Inc.46



47

Customer Impact

• Assurance operations are in control• Product is safe for patients• Company is reliable• Problems are addressed and solved• Company is leader in industry

48



Summary• Batch Release testing reflects a “snapshot” of the

quality attributes required for product release• Although sterility testing is required, the “true”

sterility of a batch is assessed through:o Sound environmental/personnel monitoring programo Personnel training and strong manual aseptic processing techniqueo Robust cleaning, disinfectant & sanitization processeso Media fill resultso Proper SOPso Equipment IQ/OQ/PQo Method validation/verificationo Dynamic smoke studieso Proper Facility Maintenanceo Particulate monitoring

49

50

Batch Release Testing Requirements PharMEDium Lunch and...

Documents

Transcript of Batch Release Testing Requirements PharMEDium Lunch and...