REPUBLIC OF PANAMÁ MINISTRY OF HEALTHEXECUTIVE DECREE No. 340 (August 27, 2007 )"Which modifies Chapter V, Title II of Executive decree 178 of July12, 2001, regulating Act 1 of January 10, 2001, on drugs and otherproducts for human health "THE PRESIDENT OF THE REPUBLIC, by the constitutional andlegal authority invested in him,CONSIDERING:That Act 1 of 10 of January 10, 2001, on drugs and other productsfor human health, establishes a mandatory health registration andbatch control for biological products;That it is an essential function of the National Direction of Pharmacyand Drugs of the Ministry of Health to watch over the efficacy,quality and safety of pharmaceutical products marketed in ournational territory;That, as established in number 3, article 17 of Act 1 of 10 of January10, 2001, the Technical Consulting Commission of the NationalDirection of Pharmacy and Drugs includes among its functions topropose, for consideration by the Health Authority, projects forregulation regarding efficacy testing, formulation changes, stabilitystudies, bio- engineering products, therapeutic equivalence, clinicaltrials and any other required by the Authority;That number 6, article 25 of Act 1 of 10 of January 10, 2001empowers the Health Authority to regulate products requiringpresentation of clinical trials as a basic requirement for healthregistration;That article 45 of the Executive Decree 6 of February 21, 2005,which regulates Chapter IV Title II of Act 1 of 10 of January 10,2001, regarding therapeutic equivalence, states that the HealthAuthority will define specific regulation to establish theexchangeability of biological and biotech products;That, in light of current scientific knowledge, it is impossible toestablish exchangeability of biotech products, making it necessary toadapt the requirements for the health registration of these products,
to guarantee their efficacy, safety and quality.DECREES: Article 1. Chapter V Title II of Executive Decree 178of July 12, 2001, is modified to read as follows:CHAPTER V HEALTH REGISTRATION OF BIOLOGICALAND BIOTECH PRODUCTS SECTION I OF BIOLOGICALPRODUCTSArticle 69. To obtain a health registration for biological products, theregulations stated in Section 1, “Basic Requirements” of Chapter I,"Process to obtain a health registration", of Title II, "Of Drugs andPharmaceutical products", of Executive Decree 178, must beobserved, in addition to compliance with what the Expert Committeeon Biological Products of the World Health Association hasestablished, and, in applicable cases, norms set by other regulatoryauthorities or organisations, such as the US Food and DrugAdministration (FDA), International Conference for Harmonisation(ICH) and the European Medication Evaluation Agency (EMEA).Article 70. Monographs of biological products, in addition to whathas been stated in Article 14 of Executive Decree 178, shouldindicate the following: a) Quantitative product descriptionexpressed in mass, in international units, biological activity units, orprotein content (if possible), according to the type of product. Whena diluent is present, this must be described (this information must beincluded in the secondary package label).b) Specifications for sources and techniques or procedures used toobtain it. c) Procedures used to endure as mush as possible theabsence of potentially pathogenic agents, which could be transmittedthrough this type of medication (precaution for cross-contamination). d) Controls developed during the manufactureprocess.e) Information on precautions that must be taken by people handlingor manipulating them, as well as those that must be observed bypatients. f) Information about how to dispose of waste products.Article 71. In the secondary package label, besides requirementsstated in Article 38 of Executive Decree 178, the following shouldbe described: a) The nature and number of excipients adjutants,
preservatives and/or any other added substance that might cause anadverse reaction.b) The dose and number of doses contained per package, and thesource. c) The diluent used for reconstitution (when applicable). d)Precautions and warnings as corresponds. e) Symbols and phraseswith warnings about the need for cold storage.SECTION II OF BIOTECH PRODUCTSArticle 71-A. Biotech products for human consumption are definedas biological protein products developed through geneticengineering, obtained using recombinant nucleic acid (DNA andRNA) combination techniques, monoclonal antibodies andothers. Article 71-B. To obtain a Health Registration for biotechproducts, the following is required:a) A formal request presented by an attorney. b) Certificate ofPharmaceutical Product, World Health Organization type, issued bythe health authority of the country of origin or Certificate of FreeSale and corresponding Certificate of Good ManufacturingPractices, both issued by the health authority of the country oforigin. c) Labels and packaging d) Monograph of the product tobe registered e) Samples f) Quali-quantitative formula g)Analysis method h) Certificate of Analysis i) Specifications ofsources and techniques or procedures used to obtain the activeprinciple j) Process for manufacturing the finished product, andproduct specifications to guarantee batch-to-batch uniformity k)Procedures used to ensure as much as possible the absence ofpotentially pathogenic agents or immune reactions l) Analyticalpatterns when required m) Product stability studies. Thoserequiring reconstitution must present stability studies before andafter reconstitution n) Conditions for storage, distribution andtransportation. o) Clinical trials showing safety, efficacy andquality of the product, or comparative trials versus the innovatorproduct p) Risk management programme and drug surveillanceplan q) Prior control r) Approval by a qualified pharmacist; it canbe the Regent Pharmacist s) Approval by the National PharmacistCollegeArticle 71-C. Clinical trials mentioned in point "o" of article 71-B of
this Executive Decree should be phase I, II and III clinical trials. Asfor comparative trials, these will include clinical, non-clinical andquality aspects, in order to determine its similarity to the innovator.Article 71-D. The National Direction of Pharmacy and Drugs willtake, as a reference for assessing clinical and comparative trials,recommendations from the Expert Committee on BiologicalProducts of the World Health Association, and technical guidelinesfrom other regulatory authorities and organisations, e.g. the US Foodand Drug Administration (FDA), the International Conference forHarmonisation (ICH) and the European Medication EvaluationAgency (EMEA).Article 71-E. Monographs of biological products, in addition to whatis stated in article 14 of Executive Decree 178, should indicate thefollowing:a) Quantitative product description expressed in mass, ininternational units, biological activity units, or protein content (ifpossible), according to the type of product. When a diluent ispresent, this must be described (this information must be included inthe secondary package label). b) The nature and amount ofexcipients and any other substance that might cause an adversereaction.c) Sources of raw materials d) Instructions for preparation,management and administration of the product e) Information abouthow to dispose of waste products f) Storage and transportationconditionsArticle 71-F. In the secondary package label, besides requirementsstated in Article 38 of Executive Decree 178, the following shouldbe described: a) The dose and number of doses contained perpackage b) The diluent used for reconstitution (when applicable)c) Precautions and warnings as corresponds d) Symbols andphrases with warnings about the need for cold storage.Article 71-G. For import or marketing, the Certificate of Analysiswill be required for each batch of product, issued by the personresponsible for Quality Assurance for the manufacturing lab orlicense holder.
Article 71-H. Biotech products that already have registrations andthose that have already started the registration process, which havenot presented clinical trials, must present them as stated in point "o"of article 71-B of this Executive Decree, within sixty (60) calendardays. Not complying with this requirement will be a cause forsuspending the health registration.Article 71-I. All license holders of biotech products alreadyapproved or undergoing approval must present a risk managementprogramme and a drug surveillance plan within 60 calendar days,which must consider all risks identified during product developmentand potential risks during use.Article 2. This Executive Decree is valid starting on the date of itspublication in the Official Legal Journal. Issued in Panama City,August 27, 2007.LET IT BE COMMUNICATED AND OBSERVEDCAMILO A. ALLEYNE Ministry of HealthMARTIN TORRIJOS ESPINO President of the Republic