asean pharmaceutical harmonization guidebook 2013

8/10/2019 ASEAN Pharmaceutical harmonization guidebook 2013

http://slidepdf.com/reader/full/asean-pharmaceutical-harmonization-guidebook-2013 1/39

Pharmaceuticals & HealthcareAsia Pacific

ASEAN PharmaceuticalHarmonizationASEAN Economic Community



Baker & McKenzie's ASEAN PharmaceuticalHarmonization Guide



i

Editors' Note

Dear Valuable Clients,

ASEAN has the potential to become a key driver of the globaleconomic structure. With a total population of about 600 million

people, a combined GDP of US$ 2.1 trillion, an abundance of naturalresources and a well-educated workforce, regional economicintegration into a single market and production base will boostASEAN's competitive edge. As we move closer to the establishmentof the ASEAN Economic Community ("AEC") in 2015, the freer flow

of capital, goods, services, investment and people may substantiallychange the way we do business and interact with our neighboringcountries.

To achieve the ASEAN's objectives, barriers such as the differentlaws, rules, regulations and standards governing goods and servicesneed to be eliminated. As a result, a long-term, concerted effort toharmonize different laws and standards was put in place with 13

sectors identified as areas of importance. Healthcare, including pharmaceuticals and other relevant products, is one of these identifiedsectors, where efforts to achieve harmonization are to be concentrated.

Baker & McKenzie, a law firm entrenched in the ASEAN, has rolledout several AEC Pharma initiatives, including seminars, publicationsand other communications, in response to this industry trend.

The AEC Seminar – Spotlight on the Pharmaceutical Industry brought together key regulatory authorities, investment specialists and pharmaceuticals & healthcare clients to talk about current updates,insights, opportunities and threats surrounding the AEC efforts. Thefirst leg of many took place in Bangkok in 2012, to be followed bysimilar seminars in Manila, Singapore and Kuala Lumpur in 2013.



ii

This ASEAN Pharmaceutical Harmonization Guidebook addressesfive key AEC harmonization issues and aims to provide informationon how to navigate your business through the ASEAN pharmaceuticalharmonization process. Included in the guidebook are majority of theASEAN member countries, namely, Cambodia, Indonesia, Lao PDR,Malaysia, Myanmar, Philippines, Singapore, Thailand, and Vietnam.

We would like to extend our gratitude to all the contributors,especially correspondent law firms, namely Sciaroni & Associates and South East Asia Law Office, whom we have partnered with forthe Cambodia and Lao PDR chapters, respectively.

ASEAN has proven that it can endure economic challenges. This fact,along with regional integration efforts, has not gone unnoticed byinternational corporations and investors. An integrated ASEANmarket, particularly in the pharmaceuticals & healthcare industry,with harmonized standards, registration and evaluation, mutualrecognition of qualifications and cross-border cooperation, will propelcompanies to become more prominent players in the global landscape.

We hope that our seminars and publications serve as a useful resourceand we look forward to engaging you more on the AEC as we spotopportunities and help your company gain the first-mover advantage.

Yours truly,Peerapan Tungsuwan

PartnerHead, Asia Pacific Pharmaceutical & Healthcare Industry Group



iii

Contributors

Baker & McKenzie

INDONESIA

Daru Lukiantono+62 21 515 [email protected]

Cahyani Endahayu+62 21 515 4893 [email protected]

MALAYSIA

Kherk Ying Chew

+60 3 2298 7933

[email protected]

Sonia Ong

+60 3 2298 7931

[email protected]

MYANMAR

Saw Yu Win

+66 2 636 2000 X6001

[email protected]

PHILIPPINES

Christina Macasaet-Acaban+63 2 819 4947

[email protected]

Charles Veloso

+63 2 819 4954

[email protected]

SINGAPORE

Andy Leck

+65 6434 2525

[email protected]

Ren Jun Lim+65 6434 2721

[email protected]

mailto:[email protected]






iv

THAILAND

Peerapan Tungsuwan

+66 2 636 2000 X4333 [email protected]

Prim Uditananda

+66 2636 2000 X4330 [email protected]

VIETNAM

Yee Chung Seck

+84 8 3520 2633

YeeChung.Seck

@bakermckenzie.com

Minh Ha Vu

+84 8 3520 2664

MinhHa.Vu

@bakermckenzie.com

Correspondent Law Firms

CAMBODIA

Bretton SciaroniSciaroni & Associates

+855 (23) 21 [email protected]

LAO PDR

Kitchrat Kontain

South East Asia Law Office+856 980 [email protected]




















Table of Contents

Editors' Note ......................................................................................... i

Contributors ........................................................................................ iii

ASEAN Pharmaceutical Harmonization ............................................. 1

AEC Pharmaceutical Questionnaire .................................................... 3

Cambodia ...................................................................................... 5

Indonesia ....................................................................................... 8

Lao PDR ..................................................................................... 12

Malaysia ...................................................................................... 14

Myanmar ..................................................................................... 17

Philippines .................................................................................. 20

Singapore .................................................................................... 24

Thailand ...................................................................................... 27

Vietnam ....................................................................................... 30



Baker & McKenzie ASEAN Pharmaceutical Harmonization 1

ASEAN Pharmaceutical Harmonization

In 2015, the ten countries which form ASEAN ("Association of

Southeast Asian Nations") will implement the ASEAN EconomicCommunity ("AEC") with the goal of creating a common economiccommunity in Southeast Asia, characterized by a single market and

production base. The establishment of this community has the potential to substantially change the way we do business and interactwith our neighboring countries.

In order to achieve the ASEAN's objectives, there is a need to

eliminate the barrier of having different laws, regulations andstandards governing goods and services. Thirteen sectors have beenidentified as areas of importance, where efforts to achieveharmonization should be concentrated. The Healthcare industry,including pharmaceuticals and other relevant products, has been

particularly identified as one of these 13 sectors.

The ASEAN Pharmaceutical Product Working Group ("PPWG"), the

regulatory body responsible for overseeing the ASEAN harmonizationefforts, has formally stated the following objective:

"To develop harmonization schemes of pharmaceutical regulations of

the ASEAN member countries to complement and facilitate the

objective of AFTA, particularly, the elimination of technical barriers

to trade posed by these regulations, without compromising drug

quality, safety and efficacy."

Through harmonization efforts, the PPWG envisions an ASEAN pharmaceutical product , for which the same regulatory requirementswould apply for all ASEAN member countries. Its developmentwould encourage increased supplies by multinational companies to theASEAN region and presumably, increased supplies between members.



2 ASEAN Pharmaceutical Harmonization Baker & McKenzie

If an ASEAN pharmaceutical product is achieved, ASEANmanufacturers could have renewed unity and coherence as well as the

benefits of cost savings and greater economies of scale. These shouldenable them not only to supply the needs of ASEAN markets morequickly and effectively, but also to compete more vigorously in thewider market of ASEAN +3 (i.e. ASEAN and its key partners, Japan,South Korea and China).

Harmonization is the key to the success of the AEC. With theestablishment of the AEC, the ASEAN Free Trade Agreement("AFTA") and the creation of the ASEAN pharmaceutical product,there lies opportunities and challenges, especially for the

pharmaceutical and healthcare industry.

The ASEAN Pharmaceutical Harmonization Guidebook aims to provide you an overview of the key harmonization issues in the pharmaceutical industry for the various ASEAN jurisdictions, namelyCambodia, Indonesia, Lao PDR, Malaysia, Myanmar, Philippines,Singapore, Thailand and Vietnam.




AEC Pharmaceutical Questionnaire

To address the key harmonization issues in the pharmaceuticalindustry, each of the ASEAN member countries responded to thesefive questions:

1) What is the definition of a"new drug"?

New drugs are defined differentlyin the various ASEAN countries.For instance, Thailand andCambodia have 7 "new drug"

categories, while other countrieshave 2 or 3 categories only. It isimportant to identify andunderstand how new drugs aredefined for product registrationand/or application purposes.

2) What are the current

requirements and timelinesfor pharmaceutical productregistrations?

The ASEAN has initiated

pharmaceutical harmonizationefforts, including thedevelopment of the ACTR andACTD format for productregistration documents. However,not all countries are at the same

pace in terms of implementation.While some countries have fullyimplemented the ACTR/ACTDformat, other countries have notgone so far as strictly requiringthe ACTR/ACTD forsubmissions.

3) Have the ASEAN CommonTechnical Requirements("ACTR") and ASEANCommon Technical Dossiers

("ACTD") beenimplemented? If not, whencan it be expected?




4) What are the requirements for pharmaceutical facilities?

In terms of the registration of pharmaceutical facilities,compliance with thePharmaceutical InspectionCooperation Scheme ("PIC/S")standards is the end goal of theASEAN harmonization. Althoughsome countries have alreadyenforced this, not all countrieshave fully adopted the PIC/Scompliance requirement.

5) Will there be a revision ofapplication files, which werenot in accordance to theACTD format?

Since not all ASEAN countrieshave fully implemented theACTR/ACTD format fordocuments, for some countries,revisions for previous productregistrations may be required.The desired outcome of theASEAN pharmaceuticalharmonization efforts is to have areview and/or revision ofapplication files every five yearsto ensure product quality andvalidity. This differs from thecurrent status for the variouscountries as some productlicenses do not expire.

To navigate your business through the ASEAN pharmaceuticalharmonization process, the responses to these five AEC questions aidin identifying where the various ASEAN countries are in terms ofimplementation as well as managing the needed preparations for

product registration submissions.




Cambodia

1. What is the definition of a "new drug"?Cambodia follows practices similar to other ASEAN countries,such as Thailand.

According to the Department of Drugs and Food, a new drugrefers to drugs having at least one of the following qualities:

1) new chemical entity

2) new indication

3) new delivery system that affects bioavailability/bioequivalence ("BA/BE")

4) new route of administration

5) new dosage form

6) new strength

7) new combination of:

i. new chemical entities and new derivatives

ii. two registered chemical entities or more but not the sameas combination drugs already registered

iii. combination drugs already registered but of differentstrength




2. What are the current requirements andtimelines for pharmaceutical productregistrations?

Pharmaceutical product application files (innovative drugs andgeneric drugs) must be submitted following ACTR and ACTD.The timeline for registration of an innovative drug isapproximately three months and the timeline for registration of ageneric drug is approximately six months, starting from the daythe FDA issues an actual acknowledgement number.

3. Have the ACTR and ACTD beenimplemented? If not, when can it beexpected?

On 1 March 2010, the ACTR/ACTD was implemented inCambodia.

Cambodia does not have an actual trial period but began voluntary

submission in 2008.

4. What are the requirements forpharmaceutical facil ities?

Local pharmaceutical manufacturing facilities must comply withGood Manufacturing Processes ("GMP") standards (refer toPIC/S), and must undergo training by the Ministry of Health.

However, according to the Department of Drugs and Food,facilities established overseas need to submit full documentation,including the Plant Master File, Plant Layout, latest GMPAssessment Report and latest GMP Certificate as well as otherdocuments for consideration for certifying overseasmanufacturing facilities.




5. Will there be a revision of application fi les,which were not in accordance to the ACTDformat?

According to the Department of Drugs and Food, starting March2010, pharmaceutical product licenses of currently registered

products must be revised according to the ACTR/ACTD ( Part I

and II ) format. A bioequivalence document must be submittedalong with the Quality documents for those Generic drugs in theList of Molecules required for Bioequivalence Study and Qualitydocuments. The Non-clinical document ( Part III ) and Clinical

document ( Part IV ) must also be submitted for the registration of New Chemical Entities ("NCE") and Biotech products.

Applications in the revised format may retain the existingregistration numbers. The result is that an application file willneed to be revised every five years as in other ASEAN countries.




Indonesia

1. What is the definition of a "new drug"?A "new drug" is a drug with a new active chemical entity, newadditive chemical, new dosage form/new route of administration,new strength, or new combination that has not been approved inIndonesia.

2. What are the current requirements and

timelines for pharmaceutical productregistrations?

Before registering drugs, the registrant should go through a pre-registration process. A pre-registration process is conducted inorder to filter drug registrations, decide on the registrationcategory, evaluation line, evaluation cost, and decide on thedocuments needed for drug registration.

The registration takes most time in the evaluation process,depending on which evaluation line the drugs should go through.There are 4 evaluation line categories, which are:

1) Forty (40) days line for:

a) Registration of minor variations that need approval;

b) Registration of drugs specialized for export

2) One hundred (100) days line for:

a) Registration of new drugs and biology products indicatedfor serious illness therapy that:

i. threatens human life (life saving), and/or

ii. is easily contagious to other people, and/or




iii. does not have or there is a lack of choice for safe andeffective therapy;

b) Registration of new drugs and biology products, whichare, based on justification, indicated for serious and rareillnesses (orphan drugs);

c) Registration of new drugs and biology products for publichealth programs;

d) Registration of new drugs and biology products, whichhave been through a development of new drug process

that is developed by a pharmacy industry or researchinstitution in Indonesia with all phases of the clinical testsconducted in Indonesia;

e) New registration of essential generic copy drugs whichare completed with supporting documents for programneeds or supporting data as a generic drug;

f) New registration of copy drugs with electronic

information standards ("Stinel"), or

g) Registration of major variations of new indications/new posology for drugs, intended for as mentioned in 2a, 2b,2c and 2d;

h) Registration of major variations which are not included in

2g.

3) One hundred and fifty (150) days line for:

a) New registration of new drugs, biology products, andregistration of major variations of new indications/new

posology that has been approved in countries applying theharmonized evaluation system and in countries with wellknown evaluation systems.




b) New registration of new drugs, biology products, andregistration of major variations of new indications/new

posology that has been approved in at least three countrieswith well known evaluation systems.

c) New registration of copy drugs without Stinel.

4) Three hundred (300) days line are for new registration of newdrugs, biology products, similar biology products, orregistration of major variations of new indications/new

posology that are not included in the evaluation line stated initem 2 and 3.

After submitting the registration form containing informationfrom the pre-registration process and enclosing the relevantdocuments, the Head of the National Agency of Drug and FoodControl ("BPOM") will decide whether to accept or decline thedrug registration. In practice, it may take 12 to 18 months forBPOM to issue a pre-market approval, starting from the dayBPOM issues an acknowledgement letter stating that the

application letter and the supporting documents have beencompletely submitted.


ACTD has been implemented since 12 October 2011 through the

enactment of 2011 BPOM regulation on Criteria and Procedure ofDrugs Registration, which results in all drug registrations tofollow ACTD format as of that date. Whereas ACTR has beenimplemented since December 2011 by the Indonesian governmentthrough conducting national workshops and providing capacity

building.





All pharmaceutical facilities must acquire a PharmaceuticalIndustry License. Starting 9 April 2012, all pharmaceuticalfacilities must also comply with the updated requirement of GMP(refer to CPOB) proven by the GMP Certificate, which is valid for5 years.

5. Will there be a revision of application fi les,which were not in accordance to the ACTD

format?

Application files which were submitted for registration before 12October 2011 will still be processed based on the old format andthose which are submitted after such date will be processed basedon the ACTD format.




Lao PDR

1. What is the definition of a "new drug"?"New drugs" refer to drugs with the following qualifications:

1) Modern drugs or any traditional medicine, resulting in positive effect

2) Not completely defined and mentioned in internationalmedical documents

3) Not registered in its country of origin

4) Registered for less than five years

5) Differs in formula, method of use, form, and packing fromdrugs that have been registered


Registration of a pharmaceutical product requires submitting anapplication form and supporting documents following ACTR andACTD to the Department of Food and Drug ("FDD").Registration of a pharmaceutical product normally takes

approximately six months upon the FDD confirming that theapplication and all supporting documents have been duly received by the FDD.





The trial period for voluntary submission started in 2009. FromAugust 2011 onwards, the FDD has gradually imposed that

pharmaceutical application files must follow ACTR/ACTD.


Local pharmaceutical manufacturing facilities must comply withGMP standards. For the overseas facilities that do not complywith the GMP standards, they are required to submit themanufacturing and product information to the FDD.


It is not clear whether the application files approved prior toAugust 2011 must be revised. However, it is obvious that allapplications filed from August 2011 onwards will follow ACTRformat, in which such applications are subject to be revised fromtime to time in accordance with the ACTR format.




Malaysia

1. What is the definition of a "new drug"?The Drug Registration Guidance Document ("DRGD") issued bythe National Pharmaceutical Control Bureau ("NPCB") of theMalaysian Ministry of Health defines "New Drug Product" or"NDP" as one which has not been registered in accordance withthe Control of Drugs and Cosmetics Regulations 1984("Regulations").

An NDP may fall under any one of the following categories:

1) New chemical entity (an active moiety that has not beenregistered in any pharmaceutical product) orradiopharmaceutical substance (a radionucleotide ligand orthe coupling mechanism to link the molecule and theradionucleotide that has not been registered in any

pharmaceutical product).

2) New combination product - a new pharmaceutical productcontaining two or more drugs that are physically, chemicallyor otherwise combined or mixed and produced as a single

pharmaceutical product, in a combination that has not beenregistered in any other pharmaceutical product.

3) Supplemental product - a new pharmaceutical productcontaining a drug that has been previously registered as a

pharmaceutical product but differing in properties with regardto safety and/or efficacy from the product that has been

previously registered.





Applications for registration of pharmaceuticals must besubmitted online to the Drug Control Authority ("DCA") via theQUEST 3 system. Registration takes between 210 - 245 workingdays from the date of final and complete submission of theapplication to the NPCB. The registration is valid for five (5)years or such other period as specified in the registrationcertificate.


Yes, the DRGD incorporates the ACTR and ACTD.

4. What are the requirements for

pharmaceutical facil ities?

Compliance with the DCA's GMP guidelines is a prerequisite forthe application of a manufacturing license, as well as productregistration. 'Manufacturing' is defined under the Regulations toinclude (i) the making or assembling of the product, (ii) theenclosing or packaging of a product in any container in a formsuitable for administration or application, and the labeling of the

container, and (iii) the carrying out of any process in the course ofany of the foregoing activities.

The DRGD states that a manufacturing site should comply withcurrent GMP standards. Local manufacturing sites are subjected to

pre-licensing inspections and for manufacturing sites outsideMalaysia, certification by the competent authority is sufficient.However, the DCA reserves the right to conduct an inspection onany manufacturing site.





There is no confirmation from the DCA whether applicationssubmitted prior to the implementation of ACTD and ACTR thatare not in ACTD format must be revised to comply.




Myanmar

1. What is the definition of a "new drug"?Drug is defined under the National Drug Law as a substance foruse, whether internal or external, in the diagnosis, prevention andtreatment of disease, birth control or for any beneficial effect inhuman beings and animals.

"New drug" is not defined specifically in the National Drug Law.The Myanmar Food and Drug Administration ("FDA") requires

updating changes to registered drugs to be made only with theapproval of the FDA. For example, changes to registered drugssuch as relevant data or findings from studies used as basis for the

justification of change, significant effect of changes to thespecification of drugs, changes to strength and dosage form.


Drug registration applications must be filed to the FDA in a form(Form 1 Registration) prescribed by the FDA following ACTDfor the registration of pharmaceuticals for human use.

Enquiring and getting approval of the FDA may take around sixmonths after submission of the completed Form 1 Registration

and documentation for common, established drugs, andapproximately nine months for less common drugs and non-newchemical entities, and approximately 12 months for new chemicalentities.





According to the current practice in applying for registration ofdrugs, the FDA mandates that the standard ACTD has to be usedin connection with complete information of drugs accompanyingForm 1 Registration, when submitting them to the FDA.Therefore, ACTD has been referred to by the FDA to be strictlycomplied with.


GMP applies to the products which are categorized as medicine,medical equipment, cosmetics or sanitation products in Myanmar.Pursuant to the National Drug Law, the Myanmar Food and DrugBoard of Authority can, among others, determine good practicesfor assurance of quality in respect of manufacturing, clinical tests

and laboratory analyses of the pharmaceutical raw material orregistered drug and all matters relating to drugs.

The National Drug Law requires a person who has been grantedthe right to manufacture, import, export, store, distribute or sell

pharmaceutical raw material or registered drug to abide strictly bythe order, directive and conditions issued by the Myanmar Foodand Drug Board of Authority in respect of quality assurance of thedrug.

Moreover, according to " A Guideline on Drug Registration

Application (revised in February 2009)" prescribed by the FDA(the "Guideline"), GMP certificate of manufacturing plant is alsorequired to be submitted to FDA, together with other relevantdocuments such as: a) a product certificate issued by theregulatory authority of its own country indicating that the productis authorized to be sold in country of origin, b) properly endorsed

photocopy of valid manufacturing license, etc. Please also refer to




answer in item 2, regarding good practices in manufacturing anddrug quality control.


The Guideline mandates that the ACTD format has to be strictlyobserved when applying for registration of drugs. The FDA doesnot accept applications for registration of drugs which are not inconformity with ACTD format.




Philippines

1. What is the definition of a "new drug"?A "new drug" refers to:

1) any drug which is not generally recognized, among expertsqualified by scientific training and experience to evaluate thesafety of drugs, as safe for use under the conditions

prescribed, recommended, or suggested in the labelingthereof.

2) any drug, the composition of which is such that said drug, as aresult of investigations to determine its safety for use undersuch conditions, has become so recognized, but which has not,otherwise than in such investigations, been used to a materialextent or for a material time under new conditions.

The term "new drug" shall include drugs: a) containing a newly

discovered active ingredient; b) containing a new fixedcombination of drugs, either by molecular or physicalcombination of drugs; c) intended for new indications; d) anadditional new mode of administration; or e) in an additionaldosage or strength of the dosage form, which meets the conditionsas defined under the new drug.

2. What are the current requirements and

timelines for pharmaceutical productregistrations?

Applications for registration of pharmaceutical products must besubmitted to the Food and Drug Administration ("FDA") inaccordance with the ACTD format. In addition, the followingdocuments must generally be submitted:




1) Notarized Letter of Application;

2) Form No. 8, as prescribed by the FDA;

3) Distributorship Agreement over the product to be distributed /imported;

4) Copy of valid License to Operate;

5) Unit Dose and Batch Formulation;

6) Technical specifications of all raw materials;

7) Certificate of Analysis of all active raw materials from themanufacturer of the active raw material and from themanufacturer of the finished product;

8) Technical specifications of the finished product;

9) Certificate of Analysis of the finished product;

10) Master manufacturing procedure, production equipment,sampling and in-process controls, and master packaging procedure;

11) Assay and other test procedures, including assay with dataanalysis;

12) Stability studies;

13) Representative sample in market or commercial presentation;

14) Labeling materials, with actual color text;

15) Bioavailability / bioequivalence studies, where applicable;

16) Dissolution profile for certain drugs;




17) For new drug applications, a copy of FDA's approval on pre-clinical, clinical and protocol for Monitored Release, therationale of Fixed Dose Combination Product (if applicable),and Post-Marketing Surveillance ("PMS") or Letter ofExtension of Monitored Release Status (if applicable);

18) For imported products, original Certificate of PharmaceuticalProduct ("CPP"), issued at least one year from the date theapplication for registration was filed, or, if CPP is notavailable, Certificate of Free Sale from the country of origin,duly authenticated by the Philippine consulate of the place ofexecution, and a government certificate attesting to the

registration status of the manufacturer, duly authenticated bythe Philippine consulate of the place of execution;

19) For products contained in plastic container: generalinformation on the container, studies done on the plastic tosubstantiate claim that the product is safe to use, test

procedure and limits, and empty plastic container and closurewith corresponding proof of payment for laboratory analysis;

20) Payment of registration fee.

The approval timeline for product registration is eight to 12months, depending on the volume of work of the FDA, and theapplicant's submission of complete documentation or immediatecompliance with any additional requirements. Applications fornew drugs may take a longer period. New drug applications forgeneral use shall be issued either two or five years based on the

application of the company while renewal registrations are validfor 5 years.


The FDA issued a circular in 2007, which stated that the

ACTD/ACTR will be fully implemented by January 2009.




However, based on informal conferences with the FDA, itconfirmed that in practice, the FDA still accepts applications thatare not compliant with the ACTD/ACTR. It has beencommunicated with Philippines regulators/health authorities thatACTD/ACTR must be fully implemented by 2015.


Pharmaceutical facilities being referred to are drug establishmentsengaged in the manufacturing, importation, exportation, sale, offerfor sale, distribution, donation, transfer, use, testing, promotion,advertising, or sponsorship of health products, including thefacilities and installation needed for its activities.

Drug establishments are inspected using the PIC/S GMP Guidesas standard for Good Manufacturing Practice. On June 2012, fullimplementation of the PIC/S GMP Guides created under theASEAN Mutual Recognition Agreement ("MRA") was adopted.For compliance, a one year transition period starting from the

effectivity of the adoption was given. In addition, a drugestablishment must obtain a License to Operate from the FDA.The requirements for obtaining a License to Operate will dependon the activity the drug establishment is engaged in (asmanufacturer/repacker, trader, or importer).


format?

According to a responsible officer of the FDA, under the current policy of the FDA, no revisions are required for applications notmade in accordance with ACTD format.




Singapore

1. What is the definition of a "new drug"?There are 3 different types of new drug applications ("NDA"):

1) NDA-1: For the first strength of a product containing a newchemical or biological entity ("new" means it has not beenregistered before in Singapore);

2) NDA-2:

(i) For the first strength of a new drug product:

• containing a new combination of registered chemical or biological entities;

• containing registered chemical or biological entity/ies in anew dosage form;

• containing registered chemical or biological entity/ies foruse by a new route of administration; or

• containing registered chemical or biological entity/ies fornew indication/s, dosage recommendation/s and/or patient

population/s.

(ii) For new drug products that do not fall under the

requirements for NDA-1, NDA-3 or generic drugapplication ("GDA").

3) NDA-3: For subsequent strength/s of a new drug product thathas been registered or has been submitted as an NDA-1 or

NDA-2. The product name, pharmaceutical dosage form,indication, dosing regimen and patient population shall be thesame as that for the NDA-1 or NDA-2.





Pharmaceutical product application files must be submittedfollowing either the International Conference on Harmonization("ICH") CTD or the ACTD format. Timelines vary from 60 to270 working days, depending on whether the submission is averification, abridged or full dossier submission.

3. Have the ACTR and ACTD been

implemented? If not, when can it beexpected?

Yes, they have been implemented since December 2005.


Documentary evidence must be provided to certify that themanufacturer complies with current applicable GMP standards.Applicants must submit a GMP certificate issued by a drugregulatory agency for all drug product manufacturing sitesincluding, but not limited to, bulk product manufacturers, primary

packagers and secondary packagers.

All new overseas drug product manufacturing sites not previously

registered with the regulators before 1 April 2004 and who intendto register their Western medicinal products in Singapore will besubjected to a GMP Conformity Assessment.





Only if variation applications need to be submitted or if there arechanges to a product's efficacy, quality and/or safety.




Thailand

1. What is the definition of a "new drug"?"New drugs" refer to drugs with the following qualifications:

1) new chemical entity

2) new indication

3) new delivery system that affects

bioavailability/bioequivalence ("BA/BE")

4) new route of administration

5) new dosage form

6) new strength

7) new combination of:

i. new chemical entities and new derivatives

ii. two registered chemical entities or more but not the sameas combination drugs already registered

iii. combination drugs already registered but with differentstrength


Pharmaceutical product application files for innovative drugs andgeneric drugs must be submitted following ACTR and ACTD.The registration timelines for innovative drugs and generic drugs

are roughly around 1.5 - 2 years and 8 - 10 months, respectively,




starting from the day the FDA issues an actual acknowledgementnumber.


The trial period for voluntary submission started in 2003. On thefirst day of January 2009 onwards, pharmaceutical applicationfiles must follow ACTR/ACTD.


Local pharmaceutical manufacturing facilities must comply withGMP standards (refer to Pharmaceutical PIC/S). Therefore,overseas facilities must comply to these GMP standards as well.From 1 October 2012 onwards, new overseas facilities who havenot yet had any pharmaceutical products registered with the FDA

prior to the date, must submit Plant Master File, Plant Layout,latest GMP Assessment Report and latest GMP Certificate asdetailed in the FDA Notification on specification of applicationform, format of the Certificate and other documents forconsideration of certifying overseas manufacturing facilities dated17 October 2012.

5. Will there be a revision of application fi les,

which were not in accordance to the ACTDformat?

Currently, pharmaceutical product licenses do not expire. TheFDA will soon announce that around 20,000 application filesapproved before 31 December 2008 are to be revised according toACTR/ACTD (parts: Administrative and Quality) as an updateand obsolete products will be eliminated. These revisions may bein the form of the variations to keep the existing registration




numbers. The outcome is that an application file will need to berevised every five years as in other countries.




Vietnam

1. What is the definition of a "new drug"?"New drug" means a drug which is registered for the first time inVietnam, including:

1) drugs containing a new chemical entity; or

2) drugs with a new combination of substances which werealready circulated in Vietnam


Application dossiers for drug registration for both innovativedrugs and generic drugs must be submitted followingACTR/ACTD.

By law, the approval timeline for a newly registered drug or re-registered drug is six months from the date of submission of aduly completed application dossier. However, in practice, thisapproval process may take 8 to 12 months, depending on theMinistry of Health's ("MOH") workload.

Approval timeline for both major variation and minor variation is

two months (by law). In practice it may take 3 to 6 months,depending on the MOH's workload.

The Product registration number is valid for five years since thedate of issuance and can be renewed.





Starting 24 May 2010, all application dossiers for drugregistration must follow ACTD.


World Health Organization ("WHO") GMP is a mandatory

requirement for all local pharmaceutical manufacturers of (i)chemical drugs since 1 July 2008 and of (ii) vaccine and medical

biologicals since 1 January 2011.

GMP certificate is valid for 3 years and can be renewed.


format?

For product registration application dossiers submitted before theACTD requirement (i.e., before 24 May 2010), once the productregistration numbers are expired, the company must submit theapplication dossier under ACTD format for renewal. This includesthe data of method validation and manufacturing processvalidation.



www.bakermckenzie.com

© 2013 Baker & McKenzie. All rights reserved. Baker & McKenzie International is a Swiss Verein with

Baker & McKenzie has been global sinceour inception. Being global is part of our DNA.

Our difference is the way we think, work and behave – we

combine an instinctively global perspective with a genuinely

multicultural approach, enabled by collaborative relationships

and yielding practical, innovative advice. Serving our clients

with more than 4,000 lawyers in over 40 countries, we have a

deep understanding of the culture of business the world over

and are able to bring the talent and experience needed to

navigate complexity across practices and borders with ease.

asean pharmaceutical harmonization guidebook 2013

Documents