T&E - Analítica






PHARMACEUTICAL EQUIVALENCE

(Inhalation Medicines and Drugs)

 

 

PHARMACEUTICAL EQUIVALENCE - Qualification ANVISA: July 26, 2001.

(Qualification: Pharmaceutical Equivalence, Dissolution / Profile of Dissolution and Bioisenption)

 

   Resolution RDC No. 31 of August 11, 2010, defines the Pharmaceutical Equivalence and Dissolution Profile as follows:

 

     I.        Pharmaceutical Equivalence Study: set of physical-chemical and, where applicable, microbiological and biological tests, which prove that two drugs are Pharmaceutical Equivalents;

   II.        Comparative Dissolution Profile Study: analytical test with multiple point collections to evaluate the dissolution of a particular active substance comparing two formulations;

 III.        Pharmaceutical equivalents: are drugs that have the same pharmaceutical form, same route of administration and same amount of the same active substance, ie even the salt or ester of the therapeutic molecule, and may contain identical excipients, as long as well established for the function intended. They must comply with the same requirements of the individual monograph of the Brazilian Pharmacopoeia, preferably, or with those of other official compendia, norms or specific regulations approved / endorsed by Anvisa or, in the absence thereof, with other standards of quality and performance. Modified release forms requiring a reservoir or excess may contain the same amount of the active substance as or not provided that they release identical amounts of the same active substance in the same dose range.

 

Other concepts can be attributed to Pharmaceutical Equivalence and Dissolution Profile: Pharmaceutical Equivalence refers to a comparative "iv" (in vitro) study by conducting physico-chemical and even microbiological and biological assays between two formulations, in which one The comparative dissolution profile refers to a comparative evaluation of the dissolution of one or more active substances in a particular analytical condition and multiple points of collection for quantification (s).

 

The Analytical T & E Center, EQFAR-025, is one of the first Centers authorized by ANVISA (since 2001), with proven experience in hundreds of studies carried out and approved by the official body.

 

Experience in all dosage forms:

Experience in all dosage forms: solid, liquid (Injectable solution or suspension, temporary or extra temporary solution or suspension, syrups, Ophthalmic, Anesthetics, among others), semisolid (ointment, cream, gel) and inhalers (sprays, DPI, MDI ), Transdermal Adhesives, Vaginal Ova, Suppositories among others. It has a MICROBIOLOGICAL laboratory, to meet all the demand necessary for these studies.

Some examples of the dosage forms highlighted above:

·         Tablets

·         Creams

·         Ointments

·         Suspensions

·         Dyes

·         Granules

·         Solutions

·         Implants

·         Injectable

·         Ointments

·         Aerodispersóides (inhalers)

·         Emulsions

·         Capsules

·         Suppositories

·         Drops

·         Depot

·         Mouthpieces

·         Gels

·         Adhesives

·         Elixirs

·         Powders

·         Syrups

·         Transdemics

·         Ova

 

               I.         Immediate Release Pharmaceutical Form: pharmaceutical form in which the total dose of the active substance is readily available after administration. In vitro assays generally show mean dissolution of at least 75% of the active substance within 45 minutes. Such a pharmaceutical form may also have different and rapid dissolution types;

 

             II.         Prolonged Release Pharmaceutical Form: A dosage form exhibiting modified release in which the active substance is gradually available in the pharmaceutical form for an extended period of time;

 

           III.         Delayed Release Pharmaceutical Form: A pharmaceutical form which shows modified release in which the active substance is released at a time different from that immediately after its administration. Gastroresistant preparations are considered a delayed release form as they are intended to resist gastric fluid and release the active substance into the intestinal fluid;

 

 

Experience in all pharmaceutical embodiments, as defined in RDC 31: The final state of presentation that the active pharmaceutical ingredients possess, following one or more pharmaceutical operations performed with the addition of suitable excipients or without the addition of excipients, in order to facilitate their and to obtain the desired therapeutic effect, with characteristics appropriate to a particular route of administration;

 

The T&E Analytical Center has vast experience and qualification to handle antineoplastic drugs, satisfying all the requirements of the current legislation for products called cytotoxic as: ONCOLOGY, HORMONES in all pharmaceutical forms, among others. In this way, it has a specific room to prepare the Cytotoxics, as well as, segregated disposal.

 

The T&E Center offers a PHARMACEUTICAL EQUIVALENCE study to:

·         Pharmaceutical equivalence for Medications in all pharmaceutical forms; 

·         Equivalencia Pharmaceutica para INALATORIUM (Spray-MDI-DPI);

 

WHEN THESE STUDIES ARE REQUESTED?

·          For the registration or renewal of similar or generic medicines; 

·          Prior to the studies of pharmaceutical bioequivalence;

·          Prior to the studies of Bioisention based on the Biopharmaceutical classification system (SCB) according to RDC 37/2011;

·          Changes in manufacturing processes, change of manufacturing site or change of supplier of raw material, etc;

·          Legal actions, requirements of ANVISA, among others;

Note: follow the legislation of ANVISA that deal with the subject.

 

ANALYTICAL TECHNIQUES

IDENTIFICATION AND QUANTIFICATION

For identifications and quantifications the analytical techniques will be in function of the molecule and the analytical resources employed, among the techniques most used are:

·         Gas-phase Chromatography (GC-FID-ECD-TCD-MS-Head Space);

·         Liquid phase chromatography (UPLC or HPLC-UV / Vis; Fluorescence; ELSD);

·         LC-MS / MS: Mass Spectrometry coupled to HPLC or UPLC;

·         ICP-OES (Induced-Simultaneous and Sequential Plasma);

·         AA - (Atomic Absorption) and FC (photometry of flame), Hydride Generator.

·         DSC;

·         High Resolution Microscopy

·         Wet testing; among others.

·         Determination of peak purity using DAD.

·         Ultraviolet and Visible Light Absorption

·         IVFT - Transformed Fourier Infrared

·         Osmometry

·         Dissolver

·         Durometer

·         Refractometer

·         Friolómetro

·         Karl Fischer titulometric and coulometric - stripping furnace

·         Camera stability photo and UV light camera

·         INHALATION

o   NGI / ACI / MSLI / SPRAYTEC / PRESSURE MEASUREMENT / SPRAY PATTERN among others specific,

o   Analytical techniques of identification and quantification.

 

Note: Other techniques can be used, always depending on the structure of the molecule. Such methodologies shall be accompanied by scientific explanation and validated in accordance with the resolution in force.

 

MICROBIOLOGY

 

Microbiological analyzes for sterile, non-sterile and antineoplastic products

 

Determination of Content - Development and Validation, among other tests:

 

·         Coliformes Thermo tolerant;                  

·         Determination of content (power);

·         Search of Salmonella;           

·         Vitamin analysis;

·         Countable viable cells;                      

·         Testing in lids and containers;

·         Challenge test;                                            

·         Supports restaurant kitchens in contamination;

·         Endotoxins LAL;                                

·         Sampling and analysis of process air and packaging;

·         Fungos;

·         Process validation analysis;

·         Sterility;

·         Verification of industrial contamination;

 

The dissolution system, DISSOLUTOR, which the T&E Analytical Center offers for the tests, has the following devices:

·         USP Apparatus 1 - Rotary Basket;

·         USP Apparatus 2 - Blades; 

·         USP Apparatus 5 - Shovel on disc;

·         USP Apparatus 6 - Rotary Cylinder.

Note: apparatuses 5 and 6 are used for transdermal, adhesive, etc.

 

CUBES

 

Conventional vats are glass or polymeric, transparent or amber. The volume and shape of the vats are important for obtaining the results.

The normal tank of a dissolutor has a volume of 900mL, cylindrical open containers with hemispherical bottom.

 

·         Cube of 900mL – hemispheric fund

·         Cube of 900mL (Peek Vessel) -  internal pre-drilling bottom

·         Cube of 500mL – hemispheric fund

·         Set of mini vats and mini spades - 250 mL

 

Note: change of tank, such as Peek Vessel, ANVISA should be consulted to conduct the tests, since it has a higher intensity vortex.

 

Every study begins with a protocol and ends with a Report and Certificate as standardized by ANVISA. The methodologies adopted are preferably pharmacopoeial (Brazilian Farm, American Farm, British Farm, European Farm, Japanese Farm ..), and when none of these compendia is available, we can propose the development of a methodology for the products or use of the methodology provided by the contracting company, performing prior to the conduction of the study a total or partial validation according to RDC 166 of July 24, 2017, as well as, all other items are governed by ANVISA or international standards. The documentation: is archived in the center the provision for consultation at any time by the contractor or regulatory agency.