Guidance for Industry
PAC-ATLS:  Postapproval Changes 
Analytical Testing Laboratory Sites
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
April 1998
CMC 10 Guidance for Industry
PAC-ATLS:  Postapproval Changes 
Analytical Testing Laboratory Sites
Additional copies are available from:
Office of Training and Communications 
Division of Communications Management
The Drug Information Branch, HFD-210
5600 Fishers Lane
Rockville, MD  20857
(Tel) 301-827-4573
(Internet)  http://www.fda.gov/cder/guidance/index.htm
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
April  1998
CMC 10 GUIDANCE FOR INDUSTRY1
   
PAC-ATLS:  Postapproval Changes 
Analytical Testing Laboratory Sites
I. INTRODUCTION
This guidance provides recommendations to pharmaceutical sponsors of new drug applications
(NDAs) and abbreviated new drug applications (ANDAs) who intend to change an analytical
testing laboratory site for components, drug product containers, closures, packaging materials, in-
process materials, or drug products during the postapproval period.  Analytical testing
laboratories include those performing physical, chemical, biological, and microbiological testing to
monitor, accept, or reject materials as well as those performing stability testing.
Changes in an approved application to allow for the use of a different facility or establishment,
including a different contract laboratory, normally require FDA approval before the change is
made (21 CFR 314.70(b)).  FDA regulations at 21 CFR 314.70(a) provide that applicants may
make changes to an approved application in accordance with a guidance, notice, or regulation
published in the Federal Register that provides for a less burdensome notification of the change
(e.g., by notification at the time a supplement is submitted or in the next annual report).  This
document provides guidance on a less burdensome approach to providing notice (i.e., Changes
Being Effected (CBE) supplement) of certain postapproval changes within the meaning of 
314.70(a).
This guidance does not comment on or otherwise affect compliance/inspection documentation
that has been defined by CDER's Office of Compliance or FDA's Office of Regulatory Affairs. 
This guidance does not affect any postapproval changes other than the ones specified.  For
changes filed in a Changes Being Effected (CBE) supplement (21 CFR 314.70(c)), the FDA may,
after a review of the supplemental information, decide that the changes are not approvable.
II. DISCUSSION
An analytical testing laboratory site change can be submitted as a Changes Being Effected (CBE)
supplement2 if (1) the test method(s) approved in the application or methods that have been
1 This guidance has been prepared under the direction of the Chemistry Manufacturing Controls Coordinating
Committee, Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration (FDA).  This
guidance represents the Agencys current thinking on postapproval changes in analytical testing laboratory sites.  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.
2 Under certain sections of 21 CFR 314.70 (e.g., 314.70(b)(2)(vi)), a change in analytical testing site is
currently designated as a prior approval supplement.  However, under 21 CFR 314.70(g)(2)(ii)(A), this type of change
is a "Supplement-Changes Being Effected in 30 Days," absent extraordinary circumstances.  This guidance is intended to implemented under 21 CFR 314.70(d) are used, (2) all postapproval commitments made by the
applicant relating to the test method(s) have been fulfilled (e.g., providing methods validation
samples), (3) the new testing facility has the capability to perform the intended testing, and (4) the
new testing facility has had a satisfactory current good manufacturing practice (CGMP) inspection
within the past 2 years.  
Prior to submitting analytical testing laboratory site change supplements, an applicant should 
determine that the laboratory has the capability to perform the intended testing.  Information to
support the capability of a laboratory to perform the intended testing (e.g., comparative data,
CGMP history of performing the test, appropriate standard operating principles (SOPs),
equipment and personnel in place) should be available for FDA investigator review.  Data
demonstrating that the new testing facility can perform the analytical test(s) being transferred need
not be included in the supplement, except for biological tests.  In the case of biological tests,
comparative data from an approved analytical testing laboratory site and the new testing facility
should be included in the supplement with the exception that this information need not be
submitted for the pyrogen and bacterial endotoxin tests.   
Information about the cGMP status of a firm may be obtained by requesting a copy of the Quality
Assurance Profile (QAP) from the FDA's Freedom of Information (FOI) Office.  The QAP
reports information on the cGMP compliance status of firms which manufacture, package,
assemble, repack, relabel or test human drugs, devices, biologics and veterinary drugs.  All FOI
requests must be in writing and should follow the instructions found in the reference entitled A
Handbook for Requesting Information and Records from FDA.   An electronic version of this
reference is on the Internet at http://www.fda.gov/opacom/backgrounders/foiahand.html.
When submitting a supplement for a change in an analytical testing laboratory site, the applicant
should confirm in a written statement why a PAC-ATLS CBE supplement is appropriate (i.e., the
four circumstances listed above exist).  The supplement should also contain the name and address
of the new analytical testing laboratory site and a full description of the testing to be performed by
the new facility.  The supplement should be clearly identified in the heading and text as being filed
under PAC-ATLS.  If the proposed change in the analytical testing laboratory site does not fall
within the scope of PAC-ATLS, it is recommended that the change be filed in a prior approval
supplement.
provide for a less burdensome notification of change, under certain circumstances, for analytical testing laboratory site
changes currently requiring prior approval supplements under 21 CFR 314.70.  It is not intended to eliminate the need to
delay distribution for 30 days of those products subject to 21 CFR 314.70(g)(2)(ii)(A).
2 GLOSSARY OF TERMS
The following terms are being provided to assist the reader in using this guidance document.
Active Ingredient:   This term is used interchangeably with active pharmaceutical ingredient
(API) and drug substance.  Any component that is intended to furnish pharmacological activity or
other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of a disease, or to
affect the structure of any function of the human body, but does not include intermediates used in
the synthesis of such ingredient.  The term includes those components that may undergo chemical
change in the manufacture of the drug product and are present in the drug product in a modified
form intended to furnish the specified activity or effect (21 CFR 210.3(b)(7) and 314.3(b)).
Biological Tests:  Biological tests include animal, cell culture or biochemical based testing that
measures a biological, biochemical or physiological response.  
Component: Any ingredient intended for use in the manufacture of a drug product, including
those that may not appear in such drug product (21 CFR  210.3(b)(3)).
Drug Product:  A finished dosage form, for example, tablet, capsule or solution, that contains an
active ingredient, generally, but not necessarily, in association with inactive ingredients (21 CFR
210.3(b)(4)).
Inactive Ingredients:  Any component other than an active ingredient (21 CFR 210.3(b)(8)).
In-process Material:  Any material fabricated, compounded, blended, or derived by chemical
reaction that is produced for, and used in, the preparation of the drug product (21 CFR
210.3(b)(9)).
Satisfactory Current Good Manufacturing Practice (cGMP) Inspection:  A satisfactory
cGMP inspection is one during which (1) no objectionable conditions or practices were found
during an inspection (No Action Indicated (NAI)) or (2) objectionable conditions were found, but
corrective action is left to the firm to take voluntarily and the objectionable conditions do not
justify further administrative or regulatory actions (Voluntary Action Indicated (VAI)).
3