HUMAN DRUG CGMP NOTES

**(Volume 7, Number 3)**

# September, 1999

**(A Memo for FDA Personnel, on Current Good Manufacturing Practice For
Human Use Pharmaceuticals)**

**Issued By: The Division of Manufacturing**

**and Product Quality, HFD-320**

**Office of Compliance**

**Center for Drug Evaluation and Research**

## Project Manager: Paul J. Motise, HFD-325

This level 2 guidance document represents the agency\'s current thinking
on Current Good Manufacturing Practice for human use pharmaceuticals. It
does not create or confer any rights for or on any person and does not
operate to bind FDA or the public. An alternative approach may be used
if such approach satisfies the requirements of the applicable statute,
regulations, or both.

**IN THIS ISSUE**

Motise\'s Notebook

Policy Questions

***Does FDA approve materials of construction for equipment? For
example, are there any specific CGMP requirements regarding ferrite
content and other properties of 316L stainless steel used in storage
tanks for pharmaceutical water systems?***

***Do CGMP requirements apply to manufacturers of clinical supplies? Can
such firms be inspected for CGMP compliance?***

***Do the CGMP regulations require firms to keep as \"raw data\" results
from employee CGMP training tests?***

Case Studies

***Formulating a drug product using active ingredient overages; what can
happen when theres too much of a good thing.***

***Validation and equipment qualification; when \"identical\" really
isn\'t.***

On Stability

***1) How should the start of the expiration dating period be calculated
for new lots of drug products?***

***2) When the labeled expiration date states only the month and year
does that mean that the drug expires at the end of the specified
month?***

Gas What? (Questions on Medical Gases)

***Do the CGMP labeling control requirements apply to medical gases
packaged in cryogenic vessels?***

Toward The Electronic Government

***1)*** ***Part 11 Enforcement CPG Publishes***

***2) Internet Resource: On-line Search Engine, "Ask Jeeves!"***

Updates

***Botanicals Guidance Availability\--Not Yet.***

Attachments

Division of Manufacturing and Product Quality, Subject Contacts

*FAX FEEDBACK* (Your input requested)

**MOTISE'S NOTEBOOK**

Welcome to another edition of Human Drug CGMP Notes, our periodic
guidance memo for FDA personnel on CGMP for human use pharmaceuticals.
Your FAX FEEDBACK responses are great and we appreciate your
suggestions. You need not, however, limit the dialog to FAX FEEDBACK.
Feel free to call, write, or e-mail your comments. We also welcome brief
articles FDAers may wish to contribute. Subjects should be CGMP related
and would be especially valuable if they address emerging new
technologies.

Although the document is fully releasable under the Freedom of
Information Act, our intended readership is FDA field and headquarters
personnel. Therefore, we cannot extend our distribution list for the
paper edition to people outside the agency. The primary purpose of this
document is to enhance field/headquarters communications on CGMP issues
in a timely manner. This is a forum to hear and address your CGMP
questions, update you on CGMP projects, and help you apply real life
situations to existing policy and enforcement documents. This memo does
not supplant existing policy development/issuance mechanisms.

Appended to each edition of the memo is a *FAX FEEDBACK* sheet to make
it easier for us to communicate. In addition to FAX (at 301-594-2202),
you can reach us by interoffice paper mail, using the above address, by
phone at (301) 594-0098, or by electronic mail.

If you would like to receive an electronic version of this document via
electronic mail, see the check-off line in *FAX FEEDBACK*. We're also on
the Internet at http:/www.fda.gov/cder/dmpq.

Thanks!

*Paul J. Motise*

Policy Questions

***Does FDA approve materials of construction for equipment? For
example, are there any specific CGMP requirements regarding ferrite
content and other properties of 316L stainless steel used in storage
tanks for pharmaceutical water systems?***

Reference: 21 CFR Sections 211.63, Equipment design, size, and location,
211.72, Filters, 211.65, Equipment construction, 211.67, Equipment
cleaning and maintenance, and 211.48, Plumbing; Guide To Inspections Of
High Purity Water Systems, July, 1993.

FDA does not approve or prohibit specific equipment or materials (with
rare exceptions such as the requirements relating to asbestos filters
found at 21 CFR 211.72). A storage tank or other piece of equipment is
subject to the general CGMP requirements addressing equipment
suitability. For example, section 211.65 requires surfaces that contact
components, in-process materials, or drug products not be reactive,
additive, or absorptive so as to adversely affect product quality.
Section 211.63 requires that equipment be of appropriate design to
facilitate operations for its intended use and for cleaning and
maintenance. Section 211.67 requires firms to clean, maintain, and
sanitize equipment at appropriate intervals to prevent malfunctions or
contamination that would adversely affect product quality.

To illustrate, it\'s important that interior surfaces of a sanitary
storage tank are capable of being cleaned, sanitized, and (if needed)
sterilized. For such sanitary equipment, design provisions to prevent
backsiphonage (see Section 211.48) and stagnation are among the
attributes that prevent microbial contamination of a drug product.
Likewise, smooth interior surfaces (e.g., welds) help prevent collection
of microbial contamination and formation of a biofilm. (See the above
inspection guide for more information on biofilms.)

So choosing materials or components for any equipment involves
evaluating whether there is any potential for an adverse impact on drug
product quality. In this respect, various compatibility considerations
(e.g., leachables, interaction with formulations/sanitizers, ability of
material to withstand sterilization) can often take on the most CGMP
significance.

Ultimately, provided that such CGMP requirements are met, firms are
afforded the flexibility to select the material and grade which best
satisfies the needs of their particular application. Given this
information, it should be no surprise that the CGMP regulations do not
include specifics on what ferrite content is appropriate in stainless
steel. However, a number of references may provide a useful starting
point when researching issues such as sanitary design standards, surface
grit/smoothness, pits, folds, crevices, and steel composition (including
ferrite content). The milk industry has publications (e.g., \"3-A
Accepted Practices for Permanently Installed Sanitary Product Pipelines
and Cleaning Systems\") written jointly with the U.S. Public Health
Service regarding sanitary design. ANSI (American National Standards
Institute) also publishes documents addressing design of seamless and
sanitary piping. Such literature should be available through a search on
the American Iron and Steel Institute (1000 16th Street, N.W.,
Washington, D.C. 20036) website at www.steel.org. A search on words such
as \"seamless\" and \"weld\" at www.nssn.org will yield further relevant
references.

Contact for further information: Richard L. Friedman, HFD-322,
301-594-0095; e-mail: friedmanr@cder.fda.gov

***Do CGMP requirements apply to manufacturers of clinical supplies? Can
such firms be inspected for CGMP compliance?***

Reference: Federal Register (43 FR 45013), September 29, 1978, preamble
to the Current Good Manufacturing Practice regulations, comment 49 (at
43 FR 45029), and Guideline on the Preparation of Investigational New
Drug Products, March, 1991.

The answer to both questions is yes. The Center for Drug Evaluation and
Research may request that firms that make clinical supplies for
Investigational New Drug (IND) trials be inspected for compliance with
Current Good Manufacturing Practice (CGMP) regulations. Such inspections
may be requested on a \"for cause\" basis, or with respect to
\"treatment INDs.\" The CGMP regulations do apply to investigational new
drug products that are intended for administration to humans.

Investigational trials are typically divided into phases. Initially, at
phase 1, trials usually involve small patient populations and are
intended to evaluate the safety of the investigational product. At phase
3, trials usually consist of much larger patient populations and are
used to evaluate both safety and efficacy.

As explained in the above guideline, the degree of CGMP control needed
increases as the investigational trials near completion. An inspection
of a phase 1 clinical supplies manufacturer would be expected to ensure
that there are no added safety concerns based strictly on the failure to
follow CGMP requirements, and that sufficient documentation is available
so that the manufacturing process can be duplicated. For phase 3 trials,
the degree of CGMP compliance would approach the control required for
marketed products. For example, as explained in the guideline, at early
clinical stages only limited process validation may be possible, and
extensive in-process controls and intensive product testing may be used
to demonstrate that a process run did, in fact, produce a finished
product that meets all its specifications. As additional uniform batches
are made under replicate conditions, we expect that more comprehensive
validation will be conducted.

Investigational trials can begin 30 days after the submission of the IND
to the agency unless a clinical hold is applied by the CDER review unit.
Inspections of clinical supplies manufacturers which identify
significant CGMP noncompliance may be a basis for a clinical hold;
however, CGMP based holds are rare.

Contact for further information: Bruce W. Hartman, HFD-324,
301-827-0062; e-mail: hartmanb@cder.fda.gov

***Do the CGMP regulations require firms to keep as \"raw data\" results
from employee CGMP training tests?***

Reference: 21 CFR Sections 211.25, Personnel qualifications, and 211.34,
Consultants

No. Section 211.25 of the CGMP regulations requires that persons engaged
in manufacture, processing, packing, or holding of a drug product have
the education, training, and experience, or any combination thereof, to
perform their jobs. The regulation also requires that employees receive
training, on a continuing basis, in those aspects of CGMP that are
pertinent to their duties. However, the regulation is silent on training
records.

Note that section 211.34 requires firms to retain records of the
qualifications of consultants, along with the type of service they
perform.

In implementing section 211.25, it should be obvious that firms need
some kind of documentation regarding their employees\' qualifications.
Accordingly, during your inspections it would be reasonable to ask firms
to show you documentation of their employee qualification and CGMP
training, for your case by case assessment.

Absence of training documentation combined with clear evidence that
employees are not qualified to do their jobs would be appropriate
observation on an FDA 483. However, absence of CGMP training test score
records would not, by itself, warrant listing on the 483.

Contact for further information: Paul J. Motise, HFD-325, 301-594-0098;
e-mail: motise@cder.fda.gov

Case Studies

***Formulating a drug product using active ingredient overages; what can
happen when theres too much of a good thing.***

Reference: 21 CFR Sections 211.101, Charge-in of components, 211.165,
Testing and release for distribution, and, 211.186 Master production and
control records.

The CGMP regulations, at Section 211.101(a) require that a batch be
formulated with the intent to provide not less than 100 percent of the
labeled or established amount of active ingredient. However, this
section is silent on formulating to provide more than 100 percent (i.e.,
overages.) Nonetheless, as discussed below, other sections of the
regulations do address overages. The following case study illustrates
potential problems that can result from using formulation overages when
firms do not follow other CGMP provisions intended to ensure that
products meet established specifications**.**

A pharmaceutical manufacturer was routinely adding 10-16% overage (above
the labeled amount) of active ingredients into a tablet formulation. The
firm did this to ensure that the assay of this tablet met the label
claim near the end of its expiry period. This overage did serve to
extend the tablets shelf life. However, it also caused the product to be
superpotent upon release for distribution. Samples were collected and
analyzed at an FDA laboratory. The laboratory results demonstrated that
not only was the product superpotent, it also failed content uniformity.
Moreover, CDER medical officers advised that the degree of superpotency
posed a health hazard to consumers. Upon FDAs complaint, the court
subsequently seized the lot that was in distribution. (The firm did not
claim the goods and the court ordered the product destroyed.)

This problem was not limited to the lot seized. The firm formulated all
lots of this product with these overages, resulting in similar potency
problems with every batch. The firm\'s master formula record did not
justify its use of overages. The batch records demonstrated that the use
of overages was inconsistent from lot to lot. (The firm has since
discontinued manufacturing this product for a variety of reasons.)

During your inspections, if you encounter a firm that is formulating a
product at less than 100% of labeled active ingredient, the practice
would be a clear CGMP violation that you should consider listing as an
objectionable condition in an FDA 483. You should not automatically so
list the use of overages. When you find use of overages you need to
investigate the practice further to determine if, among other things,
the resulting product is superpotent, or otherwise outside of its
established specifications, upon its release for distribution.

Section 211.165(f) of the CGMP regulations requires that drug products
failing to meet established standards or specifications be rejected. It
would therefore be objectionable for a firm to release for distribution
a lot it had determined to be superpotent. Therefore, as part of your
investigation, determine the firms end product testing results.

Note that a firm may be able to justify its decision to use overages,
and the practice may not always result in product that is superpotent.
It is therefore important that you review the firms documentation,
especially the master production and control record. The CGMP
regulations, at section 211.186, require that the master record contain
the weight or measure of each component, along with justifications for
reasonable variations in the amount of components necessary for the
dosage forms preparation. This section also requires that the master
record contain \[A\] statement concerning any calculated excess of
component. Thus, the regulations allow for the justified use of overages
in some instances. In general, firms will have determined justifiable
amounts of excess components during the products development and process
validation.

Contact for further information: Brian G. Nadel, HFD-325; phone 301
594-0098; e-mail: nadelb@cder.fda.gov

***Validation and equipment qualification; when \"identical\" really
isn\'t.***

Reference: 21 CFR 211.100, Written procedures, deviations; Guideline On
General Principles of Process Validation, May, 1987

As explained in the 1987 validation guideline, the general requirement
for process validation is contained in section 211.100 of the CGMP
regulations which states that \"\[T\]here shall be written procedures
for production and process control designed to assure that the drug
products have the identity, strength, quality, and purity they purport
or are represented to possess.\"

The validation guideline addresses several general principles of
equipment suitability. For example, installation qualification is
described as establishing confidence that process equipment and
ancillary systems are capable of consistently operating within
established limits and tolerances. Installation qualification includes
examination of equipment design, determination of calibration,
maintenance, and adjustment requirements, and identifying critical
equipment features that could affect the process and product. Another
principle is that equipment is evaluated and tested to verify that it is
capable of operating satisfactorily within the required process
operating limits and that actual production conditions, including
\"worst case\" situations, are simulated. The guideline cautions that
\"\[I\]n assessing the suitability of a given piece of equipment, it is
usually insufficient to rely solely upon the representations of the
equipment supplier...\"

The guideline further states that each specific process should be
appropriately qualified and validated, noting the inherent danger in
relying on perceived similarities between products, processes, and
equipment.

The following case illustrates the importance of performing adequate
equipment qualification on each piece of processing equipment, and the
problems that may result when firms fail to verify equipment supplier
representations.

A pharmaceutical firm used two blenders to produce a tablet. Both
blenders were from the same equipment manufacturer, had the same model
number and same design. Although one blender was older than the other,
the supplier told the drug manufacturer that the units were
\"identical.\" The drug manufacturer took the claim at face value and
did not include the older blender as part of its process validation.

The drug company marketed about 100 lots of tablets made using the old
blender. In testing retain samples, the company found that some lots
failed the content uniformity specification.

The firm's investigation traced the out of specification lots to one of
the two \"identical\" blenders, namely the old one. The pharmaceutical
firm's own investigation found the older blender to have a slightly
smaller capacity and different RPM (revolutions per minute) operational
characteristics when run at the same settings as the newer blender.

Subsequently, the firm recalled its total production of the product it
made using the older blender. This extensive recall involved multiple
strengths of product totaling approximately one half million bottles
from U.S. and foreign consignees. The firm plans to qualify the old
blender using production size lots.

In light of this case study, during your audits of a firm\'s process
validation, it would be appropriate to determine if the firm\'s
validation protocol includes equipment qualification for all units of
significant equipment, even where multiple units are supposedly
\"identical.\" Moreover, as explained in the validation guideline, the
validation should reflect production size lots.

Contact for further information: Michael J.Verdi, HFD-301, 301-594-2456;
e-mail: verdim@cder.fda.gov

On Stability

***1) How should the start of the expiration dating period be calculated
for new lots of drug products?***

Reference: 21 CFR Sections 211.137, Expiration dating, and 211.166,
Stability Testing; Guideline For Submitting Documentation For the
Stability of Human Drugs and Biologics, February, 1987

As explained in the stability guideline, the expiration date assigned to
a new lot of finished drug should be calculated from not later than the
date of release of the lot provided that the date of release does not
exceed approximately 30 days from the start of manufacturing (i.e., from
the initial date an active, preservative, or anti-oxidant ingredient is
added to the lot). If more than 30 days have elapsed between the date of
manufacture and date of release of the lot, the expiration date should
be calculated from within 30 days of the date of manufacture of the lot,
and not the date of release.

***2) When the labeled expiration date states only the month and year
does that mean that the drug expires at the end of the specified
month?***

References: Same as above

When the expiration date on a label states only the month and year it
means that the product will have the identity, strength, quality and
purity it purports or represents to posses through the last day of the
specified month. For products that are labeled with the month and year
of expiry, when a lot is released at the beginning of the month, the
entire first month should be included in the calculation of the
expiration date. For example, a lot that has a supportable 2 year expiry
period that is released on February 10 1998 should be assigned an expiry
date of no later than January, 2000.

Contact for further information: Barry Rothman, HFD-325, 301-594-0098;
e-mail: rothmanb@cder.fda.gov

Gas What? (Questions on Medical Gases)

***Do the CGMP labeling control requirements apply to medical gases
packaged in cryogenic vessels?***

Reference: 21 CFR 210.3, 21 CFR 211 Subpart G, Packaging and Labeling
Control, Sections 211.122 to 211.137; 21 CFR Part 201, Labeling;
Compressed Medical Gases Guideline, February 1989

Yes. Although we addressed this issue in the September 1995 edition of
the NOTES, this matter continues to be an area of confusion and one of
the most frequently asked questions we receive. Therefore, it is worth
revisiting.

Medical gases are not exempt from the general labeling requirements of
21 CFR Part 201. The filling of medical gases is considered a
manufacturing operation and, as defined in 210.3, applying labeling to
containers is also a manufacturing operation. Therefore, cryogenic
vessels are subject to the labeling controls of Subpart G - Packaging
and Labeling Control, Sections 211.122 - 137. This would include all
high pressure cylinders, large dewars or cryogenic vessels, and home or
patient vessels.

Accordingly, any individual or firm filling cryogenic vessels, including
patient or home vessels, is required to apply a drug label containing
all of the required information and to follow CGMP labeling control
measures.

See the medical gases guideline for additional information regarding
labeling controls.

Contact for further information: Duane Sylvia, HFD-325, 301-594-0095,
e-mail: sylviad@cder.fda.gov

Toward The Electronic Government

***1) Part 11 Enforcement CPG Publishes***

Compliance Policy Guide (CPG) 7153.17 (Section 160.850); Enforcement
Policy: 21 CFR Part 11; Electronic Records; Electronic Signatures,
issued on May 13, 1999. The agency published a notice of availability,
and full text, of the CPG in the July 21, 1999 Federal Register (64 FR
39146.) The CPG gives a brief background on part 11, and makes the
following points:

\(1\) Legacy systems (those in place before August 20, 1997, part 11\'s
effective date). Older electronic records systems may not have reached
full compliance by 8/20/97 and their modification may take more time.
However, legacy systems are not grandfathered and FDA expects firms that
use legacy systems will begin taking steps to achieve full compliance.

\(2\) Regulatory action determinations. For all systems (legacy, too)
decisions on whether or not non-compliance merits pursuit of regulatory
action will be based on a case by case evalution. The evaluation may
include consideration of the:

> a\. Nature and extent of part 11 deviations. Deviations would be more
> signficant if they are numerous, make it difficult for FDA to audit or
> interpret data, or undermine data integrity;
>
> b\. Effect on product quality and data integrity. Lack of an audit
> trail, for example, would be highly significant when there are data
> discrepancies and individuals deny record entry responsibility.
> Likewise, lack of operational system checks that result in adulterated
> or misbranded product would be significant;
>
> c\. Adequacy and timeliness of planned corrective measures. Firms
> should have a reasonable timetable for coming into compliance, and
> demonstrate progress toward that goal. While technical controls may
> take longer to install on some older systems, FDA expects that
> procedural controls will already be in place; and,
>
> d\. Compliance history of the establishment, especially with respect
> to data integrity. A history of part 11 violations or inadequate or
> unreliable recordkeeping would make part 11 deviations more
> significant. Until firms reach full compliance, FDA investigators will
> be more vigilant to detect such problems as inconsistencies,
> unauthorized changes, and poor attribution.

\(3\) Headquarters consultation. Program monitors and center compliance
offices should be consulted before recommending regulatory actions.

\(4\) Regulatory citations. Regulatory citations should reference the
applicable predicate regulations in addition to part 11.

***2) Internet Resource: On-line Search Engine, "Ask Jeeves!"***

"Ask Jeeves!" is a relatively new search engine you may find useful in
your work. The site has two addresses (http://www.aj.com and
http:/www.ask.com). Jeeves allows you to enter a search in the form of a
question in plain English. It then parses that question, checks your
spelling, and quickly returns a page of results (hits) from several
search engines and newsgroups. Compared to keyword searches, parsing
your prose is intended to be more efficient and precise, meaning you're
supposed to get far fewer meaningless or irrelevant hits.

I asked Jeeves, "What are pyrogens?" and was impressed with the answers.
The results page displayed multiple lines of information. Each line
showed: (1) The hyperlinked name of the Internet search engine
(including Jeeve's own) that came up with one or more hit documents; (2)
the number of hit documents found; (3) the first few words (header) of
the first hit document; and, (4) an icon labeled "Ask" that links
directly to the hit document itself. When a given search engine returns
multiple documents the resulting list of headers takes the form of a
drop down menu. I found this feature to be more convenient than what
other search engines generally produce, namely a long list of documents
that can span several screens.

When you click on the Ask icon to get to a specific hit document, Jeeves
inserts an advertising banner in a frame at the top of the display. The
Internet address for the document appears in your web browser as a
combination of the Jeeves site and the destination site. These
attributes bother me, especially when I want to identify the specific
Internet address that corresponds precisely to the final document (e.g.,
for use as a reference or to store as an Internet bookmark). Click on
the words \"delete frames\" at the bottom edge of the banner to make it
disappear and make your browser display the document\'s direct address
(without the Jeeves part.) Another work-around is to click on the name
of the search engine itself, and then link to the document from that
site instead of clicking on the Jeeves Ask icon.

All in all, I was pleased with the results of my search. Among the hit
documents were the CGMP regulations, the Merck Manual, FDA's Guide to
Inspections of Dosage Form Drug Manufacturers, and a paper on bacterial
anatomy. Oh yes, there was also the following definition of pyrogens
from a web site at the University of Kansas Medical Center:

> "Pyrogens are substances that cause fever. The most important
> endogenous pyrogens, meaning that they are pyrogens that are produced
> in the body, are the cytokines interleukin-1 and TNF-alpha."

\[Consider this definition as informational, and not FDA\'s formal
definition.\]

If you try "Ask Jeeves!" I think you'll find it a useful research and
reference tool in your day to day inspectional and compliance
activities.

Contact for further information: Paul J. Motise, HFD-325; 301-594-0098;
e-mail: motise@cder.fda.gov

Updates

***Botanicals Guidance Availability \--Not Yet.***

In the prior issue of HUMAN DRUG CGMP NOTES we referenced a draft
\"Guidance for Industry, Botanical Drug Products.\" Response to the
botanicals article reflects considerable interest in this topic.
However, because FDA hasn\'t yet published the document for public
comment, its general availability will have to await that issuance. The
agency will announce its availability in the Federal Register.

As a reminder, during your inspectional and compliance work, you should
not implement draft guidances, but rather treat them as informational
until they\'ve been finalized.

Contact for further information: Brian Nadel, HFD‑325, (301) 594‑0098:
e‑mail: nadelb@cder.fda.gov

P. Motise 09/01/99

DOC ID CNOTES99.doc

# DIVISION OF MANUFACTURING AND PRODUCT QUALITY, HFD-320

**SUBJECT CONTACTS**

(All numbers in area code 301)

Active Pharmaceutical Edwin Rivera 594-0095

Ingredients Pat Alcock \"

Application Integrity Policy

Implementation/Removal LuAnn Pallas 594-0098

Data Integrity Cases Bruce Hartman 827-0062

Aseptic Processing Rick Friedman 594-0095

Tracy Roberts 594-0098

Edwin Melendez 594-2454

Barriers/Isolators Rick Friedman 594-0095

Edwin Melendez 594-2454

Biotechnology Brian Nadel 594-0098

Botanicals Manufacturing Brian Hasselbalch 594-0098

Case Management Fred Blumenschein 594-0098

CGMP Guidance Documents Paul Motise 594-0098

Cleaning Validation Russ Rutledge 594-2455

Pat Alcock 594-0095

Clinical Supplies/IND CGMP Paul Motise 594-0098

Bruce Hartman 827-0062

Computer Validation Paul Motise 594-0098

Content Uniformity Monica Caphart 594-2458

Russ Rutledge 594-2455

Electronic Records/Signatures Paul Motise 594-0098

Facility Reviews Russ Rutledge 594-2455

Foreign Inspections John Dietrick 594-0095

Impurities Rick Friedman 594-0095

Inspections/ Investigations Randall Woods 827-0065

(For Cause)

Labeling Controls (CGMP) Paul Motise 594-0098

Laboratory Issues Monica Caphart 594-2458

Russ Rutledge 594-2455

# DIVISION OF MANUFACTURING AND PRODUCT QUALITY, HFD-320

**SUBJECT CONTACTS (Continued)**

(All numbers in area code 301)

Litigation Guidance and Nick Buhay 594-0098

Support

Medical Gases Duane S. Sylvia 594-0095

NDA/ANDA Pre-Approval Randall Woods 827-0062

Inspections

Packaging Edwin Melendez 594-2454

Penicillin Cross Contamination Edwin Melendez 594-2454

Pharmacies, CGMP LuAnn Pallas 594-0098

Pre-Approval Program Melissa Egas 594-0095

Bruce Hartman 927-0062

Process Validation, General John Dietrick 594-0098

Paul Motise "

Recycling Plastic Containers Paul Motise 594-0098

Repackaging Barry Rothman 594-0098

Salvaging Paul Motise 594-0098

Stability/Expiration Dates Barry Rothman 594-0098

Sterility Issues, General Rick Friedman 594-0095

Tracy Roberts 594-0098

Edwin Melendez 594-2454

Topical Drugs Randall Woods 827-0062

Transdermals Brian Hasselbalch 594-0098

Videoconferencing Russ Rutledge 594-2455

Paul Motise 594-0098

Water Quality Rick Friedman 594-0095

Edwin Melendez 594-2454

Tracy Roberts 594-0098

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Here's my question/comment regarding
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Future editions of HUMAN DRUG CGMP NOTES should address the following
CGMP questions/issues:

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